Drug delivery device

ABSTRACT

A drug delivery device may include a housing defining a longitudinal axis and having an opening and a drug storage container including a delivery member having an insertion end configured to extend at least partially through the opening during a delivery state. The device may also include plunger moveable toward the distal end of the drug storage container to expel a drug from the drug storage container through the delivery member, the plunger including a body portion having an inner wall defining an axial chamber and an outer wall cooperating with the inner wall to define a body thickness. The device may further include a plunger biasing member disposed at least partially within the axial chamber, the plunger biasing member configured to urge the plunger toward the distal end of the drug storage container.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application claims the priority of U.S. ProvisionalApplication No. 62/908,504, filed Sep. 30, 2019, entitled, “DrugDelivery Device,” and U.S. Provisional Application No. 62/961,031, filedJan. 14, 2020, entitled, “Drug Delivery Device,” each of which isincorporated by reference.

FIELD OF DISCLOSURE

The present disclosure relates to drug delivery devices, and, moreparticularly, devices for automatically injecting a drug into a patient.

BACKGROUND

A general aversion to exposed needles, as well as health and safetyissues, have led to the development of drug delivery devices whichconceal a needle or other insertion member prior to use and whichautomate various aspects of an injection process. Such devices offer avariety of benefits as compared with traditional forms of drug deliveryincluding, for example, delivery via a conventional syringe.

Many injector systems use coil and other spring structures to provideactuation energy for functions such as needle insertion and/or fluiddelivery. The use of springs can offer benefits of simplicity and lowcost, but it may have certain limitations. For example, there is alinear relationship between force and displacement in spring actuators.To provide sufficient energy for drug delivery at the end of plungerstroke, an excessive amount of energy may be input to the system as drugdelivery commences. As another example, as higher viscosity drugs aredelivered via autoinjectors, the requisite spring forces will likelyincrease. Springs with higher spring constants may transmit more forceto the drug product and primary container. Various physicalcharacteristics of a spring may affect the spring rate, and thus thespring force, such as wire diameter of the spring, mean diameter of thespring, the number of spring coils, and the spring material. Therefore,it may be desirable and/or advantageous to include device componentsthat permit flexibility in spring design and/or that facilitate the useof springs with different physical characteristics with the remainingdevice components.

The present disclosure sets forth drug delivery devices embodyingadvantageous alternatives to existing drug delivery devices, and thatmay address one or more of the challenges or needs mentioned herein.

SUMMARY

One aspect of the present disclosure provides a drug delivery deviceincluding a housing defining a longitudinal axis and having an openingand a drug storage container including a delivery member having aninsertion end configured to extend at least partially through theopening during a delivery state. The device may further include aplunger moveable toward the distal end of the drug storage container toexpel a drug from the drug storage container through the deliverymember, the plunger including a body portion having an inner walldefining an axial chamber and an outer wall cooperating with the innerwall to define a body thickness. The device may also include a plungerbiasing member disposed at least partially within the axial chamber, theplunger biasing member configured to urge the plunger toward the distalend of the drug storage container.

The plunger body portion may have a hollow tubular shape. The plungerbody portion may be made of metal or non-metal.

The plunger may be configured to selectively rotate from an initialrotational position to a second rotational position under a biasingforce exerted by the plunger biasing member and to translate linearlytoward the distal end of the drug storage container under the biasingforce exerted by the plunger biasing member after rotating from theinitial rotational position to the second rotational position.

The device may further include a plunger guide fixed relative to thehousing, the plunger being disposed at least partially within theplunger guide. One of the plunger and the plunger guide may comprises acam and the other one of the plunger and the plunger guide may comprisesa cam follower.

The plunger may include the cam follower and the plunger guide includesthe cam, and the cam follower may be formed by at least one flangeextending radially outwardly from the plunger.

The plunger body thickness may be less than 0.6 millimeters, less than0.4 millimeters, less than 0.3 millimeters, less than 0.2 millimeters,less than 0.1 millimeters, or less than 0.05 millimeters.

Another aspect of the present disclosure provides a drug delivery deviceincluding a housing defining a longitudinal axis and having an openingand a drug storage container including a delivery member having aninsertion end configured to extend at least partially through theopening during a delivery state. The device may further include aplunger moveable toward the distal end of the drug storage container toexpel a drug from the drug storage container through the deliverymember, the plunger including a body portion having an inner walldefining an axial chamber and an outer wall cooperating with the innerwall to define a body thickness less than 0.6 millimeters. The devicemay also include a plunger biasing member coupled with the plunger andconfigured to urge the plunger toward the distal end of the drug storagecontainer.

BRIEF DESCRIPTION OF THE DRAWINGS

It is believed that the disclosure will be more fully understood fromthe following description taken in conjunction with the accompanyingdrawings. Some of the drawings may have been simplified by the omissionof selected elements for the purpose of more clearly showing otherelements. Such omissions of elements in some drawings are notnecessarily indicative of the presence or absence of particular elementsin any of the exemplary embodiments, except as may be explicitlydelineated in the corresponding written description. Also, none of thedrawings is necessarily to scale.

FIG. 1A is a perspective view of an exemplary drug delivery device inaccordance with various embodiments;

FIG. 1B is a perspective view of the drug delivery device in FIG. 1A,with a cap removed therefrom;

FIG. 1C is a perspective view of the drug delivery device in FIG. 1A, ina pre-injection configuration;

FIG. 1D is a perspective view of the drug delivery device in FIG. 1A, inan injection configuration;

FIG. 2 is cross-sectional view of the drug delivery device in FIG. 1;

FIG. 3A is an exploded assembly view of a portion, namely the drivemechanism, of the drug delivery device in FIG. 2;

FIG. 3B is an exploded assembly view of the drug delivery device in FIG.2;

FIG. 4A is a perspective view of an exemplary drug storage container foruse with a drug delivery device in accordance with various embodiments;

FIG. 4B is a perspective view of an exemplary container holder for usewith a drug delivery device in accordance with various embodiments,where the container holder is in an open position;

FIG. 4C is a perspective view of the container holder in FIG. 4B coupledwith the drug storage container in FIG. 4A, where the container holderis in a closed position;

FIG. 4D is a perspective view of an exemplary container holder for usewith a drug delivery device in accordance with various embodiments,where the container holder is in a closed position;

FIG. 4E is a perspective view of an exemplary housing for use with adrug delivery device in accordance with various embodiments;

FIG. 4F is a partial cross-sectional view of the container holder andthe drug storage container, taken around line 4F-4F in FIG. 4C;

FIG. 5A is a partial cross-sectional view of the container holder, thedrug storage container, taken around line 5A-5A in FIG. 4C, as well as apartial cross-sectional view of a distal portion of an exemplary plungerguide coupled with the container holder and the drug storage container;

FIG. 5B is a perspective view of an exemplary plunger guide inaccordance with various embodiments;

FIG. 5C is a perspective, partial cross-sectional view of the plungerguide in FIG. 5B;

FIG. 6A is a perspective view of an exemplary guard member in accordancewith various embodiments;

FIG. 6B is a perspective view of an exemplary guard extension inaccordance with various embodiments;

FIG. 6C is a perspective, partial cross-sectional, view of the guardextension, the releaser, and the plunger guide, wherein the componentsare in a pre-injection position;

FIG. 7A is a perspective view of an exemplary releaser member inaccordance with various embodiments;

FIG. 7B is another perspective view of the releaser member in FIG. 7A;

FIG. 8 is a perspective view of the plunger guide from FIG. 5B, thereleaser member from FIG. 7A, and the plunger 26 shown in FIG. 2,wherein the guide member is shown in translucent form for illustrativepurposes;

FIG. 9A is a perspective view of an exemplary plunger guide, anexemplary releaser member, and an exemplary plunger, wherein a portionof the guide member is shown in cut-away form for illustrative purposes,and wherein the drug delivery device is in a pre-injection position;

FIG. 9B is a perspective view of the components from FIG. 9A, whereinthe plunger is in a released position before axial travel by theplunger;

FIG. 9C is a perspective view of the components from FIG. 9A, whereinthe plunger is in the released position after the start of axial travelby the plunger;

FIG. 10A is a top view of the components in FIG. 9A, wherein the drugdelivery device is in the pre-injection position;

FIG. 10B is a top view of the components in FIG. 9B, wherein the plungeris in the released position before axial travel by the plunger;

FIG. 10C is a top view of the components in FIG. 9C, wherein the plungeris in the released position after the start of axial travel by theplunger;

FIG. 11A is a perspective view of the components in FIG. 9A plusadditional components, such as an exemplary guard extension, and whereinthe drug delivery device is in a pre-injection position;

FIG. 11B is a perspective view of the components in FIG. 11A, whereinthe guard extension has been moved proximally but the plunger has notbeen released;

FIG. 11C is a perspective view of the components in FIG. 11A, whereinthe guard extension has been further moved proximally and the plungerhas released but has not yet traveled axially;

FIG. 12A is a perspective view of the components in FIG. 9A, plus anexemplary guard biasing member, where the plunger is in the releasedposition after the start of axial travel by the plunger, where some ofthe components are shown in cut-away form for illustrative purposes;

FIG. 12B is a perspective view of the components of FIG. 12A, plus amore distal view of the device, where the plunger is at or near anend-of-dose release position but the releaser member is not yet at anend-of-dose position, and where the guard extension member and the guardbiasing member are removed for illustrative purposes;

FIG. 12C is a perspective view of the components of FIG. 12A, where thereleaser member is at the end-of-dose position;

FIG. 13 is a perspective view of an exemplary lock ring in accordancewith various embodiments;

FIG. 14 is a perspective view of a distal portion of an exemplary devicein accordance with various embodiments when a guard member is in apre-injection, pre-deflection state, and wherein portions of the housingare shown in cut-away form for illustrative purposes;

FIG. 15A is a perspective view of the distal portion of the device shownin FIG. 14, where the guard member is in an initial deflection stage;

FIG. 15B is a perspective view of the same device and the same stage asFIG. 15A, from a view that is approximately 90 degrees from that shownin FIG. 15A;

FIG. 16A is a perspective view of the distal portion of the device shownin FIG. 14, where the guard member further deflected distally from thestage shown in FIG. 15A;

FIG. 16B is a perspective view of the same device and the same stage asFIG. 16A, from a view that is approximately 90 degrees from that shownin FIG. 16A;

FIG. 17 is a perspective view of the distal portion of the device shownin FIG. 14, where the guard member is in a fully-deflected or nearfully-deflected position with respect to the housing, such as during aninjection stage;

FIG. 18A is a perspective view of the distal portion of the device shownin FIG. 14, where the guard member is in a fully-retracted, locked-outposition with respect to the housing, and the device is in apost-injection stage;

FIG. 18B is a perspective view of the distal portion of the device shownin FIG. 14, where the guard member is in a near fully-retracted,locked-out position with respect to the housing, and the device is in apost-injection stage;

FIG. 19A is a graph showing an exemplary force profile during theinjection process of an exemplary drug delivery device, where relativedisplacement between the device housing and the guard member is plottedalong the x-axis (in millimeters) and resistance is plotted along they-axis (Newtons);

FIG. 19B is another exemplary force profile during the injection processof an exemplary drug delivery device, similar to that in FIG. 19A;

FIGS. 20A-20G show another exemplary drug delivery device in accordancewith various embodiments;

FIGS. 21A-21F show yet another exemplary drug delivery device inaccordance with various embodiments;

FIG. 22 shows the guard member shown in FIGS. 20A-20G and FIGS. 21A-21F;

FIG. 23 shows the lock ring shown in FIGS. 20A-20G;

FIG. 24 shows the force profiles of various devices, with two of theforce profiles shown in FIGS. 19A and 19B, respectively, one forceprofile (illustrated as a dashed line) attributable to the device 400shown in FIGS. 20A-20G, and another force profile (illustrated as adotted line) attributable to the device 500 shown in FIGS. 21A-21F;

FIG. 25 illustrates a perspective view of an exemplary housing inaccordance with various embodiments; and

FIGS. 26A-26D depict another exemplary drug delivery device inaccordance with various embodiments, with FIGS. 26A and 26B illustratingdifferent perspective views of a lock ring of the drug delivery device,FIG. 26C illustrating a perspective view of a guard member of the drugdelivery device, and FIG. 26D illustrating a cutaway view of a portionof the drug delivery device.

DETAILED DESCRIPTION

The present disclosure generally relates to drug delivery devicesoperable by a user for administering a drug, or in the case where apatient is the user, self-administering a drug. Various features aredisclosed for streamlining, simplifying, automating and/or facilitatingcertain aspects of drug delivery, such as those utilized inauto-injectors, on-body injectors, or other automatic or partiallyautomatic drug delivery devices (collectively autoinjectors orauto-injectors). For example, these features may include automaticallycovering a needle in a pre-delivery and/or post-delivery state,automatically inserting a needle and/or a cannula into a user,automatically activating a drive mechanism, automatically indicating tothe user that drug delivery is complete, among other features. Althoughknown drug delivery devices incorporate a separate or independentlyoperable mechanism to realize each of its automated features, thepresent disclosure includes eliminating and/or combining at least someof these features and/or providing device components that permitflexibility in device design. For example, the device may includecomponents that permit flexibility in spring design and/or thatfacilitate the use of springs with different physical characteristicswith the remaining device components. As another example, the device mayinclude components that reduce the part number, part complexity, overallweight of the device, and/or overall complexity of the device. Forexample, the present disclosure may include a plunger moveable towardthe distal end of the drug storage container to expel a drug from thedrug storage container through the delivery member, where the plungerincludes a body portion having an inner wall defining an axial chamberand an outer wall cooperating with the inner wall to define a bodythickness. The present disclosure may also include a plunger biasingmember disposed at least partially within the axial chamber, where theplunger biasing member is configured to urge the plunger toward thedistal end of the drug storage container.

FIGS. 1-3 illustrate several views of an embodiment of a drug deliverydevice 10 for delivering a drug, which may also be referred to herein asa medicament or drug product. The drug may be, but is not limited to,various biologicals such as peptides, peptibodies, or antibodies. Thedrug may be in a fluid or liquid form, although the disclosure is notlimited to a particular state.

Various implementations and configurations of the drug delivery device10 are possible. The present embodiment of the drug delivery device 10is configured as a single-use, disposable injector. In otherembodiments, the drug delivery device 10 may be configured asmultiple-use reusable injector. The drug delivery device 10 is operablefor self-administration by a patient or for administration by caregiveror a formally trained healthcare provider (e.g., a doctor or nurse). Theexemplary the drug delivery devices shown in the figures may take theform of an autoinjector or pen-type injector, and, as such, may be heldin the hand of the user over the duration of drug delivery, but may alsoor alternatively be suitable for other drug delivery devices and/orconfigurations.

The configuration of various components included in the drug deliverydevice 10 may depend on the operational state of the drug deliverydevice 10. The drug delivery device 10 may have a pre-delivery orstorage state, a delivery or dosing state, and a post-delivery state,although fewer or more states are also possible. For example, each statemay have several sub-states or stages. The pre-delivery state maycorrespond to the configuration of the drug delivery device 10subsequent to assembly and prior to activation by the user. In someembodiments, the pre-delivery state may exist in the time between whenthe drug delivery device 10 leaves a manufacturing facility and when apatient or user activates a drive mechanism 30 of the drug deliverydevice 10. This includes the moments in time after the user has removedthe drug delivery device 10 from any secondary packaging and prior topositioning the drug delivery device 10 against the injection site. Thedelivery state may correspond to the configuration of the drug deliverydevice 10 while drug delivery, also referred to herein as dosing, is inprogress. The post-delivery state may correspond to the configuration ofthe drug delivery device 10 after drug delivery is complete and/or whena stopper is arranged in an end-of-dose position in a drug storagecontainer.

As shown in FIGS. 1A and 1B, the drug delivery device 10 includes anouter casing or housing 12. In some embodiments, the housing 12 may besized and dimensioned to enable a person to grasp the injector 10 in asingle hand. The housing 12 may have a generally elongate shape, such asa cylindrical shape, and extend along a longitudinal axis A between aproximal end and a distal end. An opening 14 (FIG. 3B) may be formed inthe distal end to permit an insertion end 28 of a delivery member 16(FIG. 2) to extend outside of the housing 12. A transparent orsemi-transparent inspection window 17 (FIGS. 1A-1B) may be positioned ina wall of the housing 12 to permit a user to view component(s) insidethe drug delivery device 10, including a drug storage container 20.Viewing the drug storage container 20 through the window 17 may allow auser to confirm that drug delivery is in progress and/or complete. Aremovable cap 19 may cover the opening 14 prior to use of the drugdelivery device 10, and, in some embodiments, may including a gripper 13(FIG. 2) configured to assist with removing a sterile barrier 21 (e.g.,a rigid needle shield (RNS), a non-rigid needle shield (nRNS), etc.)mounted on the insertion end 28 of the delivery member 16. The gripper13 may include one or more inwardly protruding barbs or arms thatfrictionally or otherwise mechanically engage the sterile barrier 21 topull the sterile barrier 21 with the removable cap 19 when the userseparates the removable cap 19 from the housing 12. Thus, removing theremovable cap 19 has the effect of removing the sterile barrier 21 fromthe delivery member 16.

As shown in FIG. 2, the drive mechanism 30 may be disposed partially orentirely within the housing 12. Generally, the drive mechanism 30 may beconfigured to store energy and, upon or in response to activation of thedrive mechanism 30 by the user, release or output that energy to drivethe plunger 26 to expel the drug 22 from the drug storage container 20through the delivery member 16 into the patient. In the presentembodiment, the drive mechanism 30 is configured to store mechanicalpotential energy; however, alternative embodiments of the drivemechanism 30 may be configured differently, for example, with the drivemechanism 30 storing electrical or chemical potential energy. Generally,upon activation of the drive mechanism 30, the drive mechanism 30 mayconvert the potential energy into kinetic energy for moving the plunger26. As best illustrated in FIG. 3A, in one embodiment, the drivemechanism 30 includes the plunger biasing member 50, a hollow rod 46 forsupporting the plunger biasing member 50, a plunger biasing member seat38, the releaser member 52, a plunger guide 60, an extender biasingmember 35, and a guard extension 37. The plunger biasing member 50 mayinclude a compression spring (e.g., a helical compression spring) whichis initially retained in an energized state. In the energized state, theplunger biasing member 50 may be compressed such that its axial lengthis shorter than it would be in a natural or de-energized state. Whenreleased, the plunger biasing member 50 may try to expand to its naturalaxial length, and as a consequence, exert a biasing force pushing theplunger 26 in the distal direction.

As best shown in FIGS. 2 and 3B, in one embodiment the device 10 includea housing 12 may include two separate and interconnected structures: arear end cap 23 (e.g., a rear cover) at the proximal end of the drugdelivery device 10; and a tubular housing 25 extending substantiallycompletely along the length of the drug delivery device 10 and definingthe opening 14. Additionally or alternatively, the housing 12 mayinclude fewer or more components, such as a two-piece tubular housinghaving front and rear portions. The tubular housing 25 may have a hollowand generally cylindrical or tubular shape, and the rear end cap 23 mayhave a generally hemispherical shape or a hollow cylindrical shape withan open end and a closed off end. In some embodiments, the rear end cap23 and the tubular housing 25, and any components to be positionedtherein, may be assembled together to define different sub-assemblies,such as the drive mechanism 30 (FIG. 3A). In some embodiments, thedifferent sub-assemblies are assembled independently of each other andthen later combined with one another, as well as with the drug storagecontainer 20, to form the fully-assembled drug delivery device 10. Incertain such embodiments, some or all of the foregoing phases ofassembly may occur in different manufacturing facilities orenvironments. In alternative embodiments, the housing 12 may beconstructed in one piece, such that the housing 12 is defined by asingle, monolithic structure that integrates a rear cap and tubularhousing in a single component.

The drug storage container 20 is disposed within an interior space ofthe housing 12 and is configured to contain a drug 22. The drug storagecontainer 20 may be pre-filled and shipped, e.g., by a manufacturer, toa location where the drug storage container 20 is combined with aremainder of the drug delivery device 10. For example, the drug 22 maybe distributed and/or provided to patients in more than one use case,such as a as a pre-filled syringe or as an autoinjector including apre-filled syringe. By utilizing the same or similar syringe componentsin either case, at least some of above steps such as filling, labeling,packaging, shipping, and distribution may be streamlined or simplifiedfor two different use cases. As a another example, in the event thatmultiple use cases utilize some or all of the same syringe components,some regulatory pathways to marketing and/or distributing the drug maybe streamlined and/or simplified for at least one of the multiple usecases.

The housing 12 may be pre-loaded with the drug storage container 20,e.g., by a manufacturer, or alternatively, loaded with the drug storagecontainer 20 by a user prior to use of the drug delivery device 10. Thedrug storage container 20 may include a rigid wall defining an internalbore or reservoir. The wall may be made of glass or plastic. A stopper24 may be moveably disposed in the drug storage container 20 such thatit can move in a distal direction along the longitudinal axis A betweenproximal end and a distal end of the drug storage container 20. Thestopper 24 may be constructed of rubber or any other suitable material.The stopper 24 may slidably and sealingly contact an interior surface 15of the wall of the drug storage container 20 such that the drug 22 isprevented or inhibited from leaking past the stopper 24 when the stopper24 is in motion. Distal movement of the stopper 24 expels the drug 22from the reservoir of the drug storage container 20 into the deliverymember 16. The proximal end of the drug storage container 20 may be opento allow a plunger 26 to extend into the drug storage container 20 andpush the stopper 24 in the distal direction. In the present embodiment,the plunger 26 and the stopper 24 are initially spaced from each otherby a gap 18 (FIG. 2). Upon activation of a drive mechanism 30, theplunger 26 moves in the distal direction to close the gap and comes intocontact with the stopper 24. Subsequent distal movement of the plunger26 drives the stopper 24 in the distal direction to expel the drug 22from the drug storage container 20. In alternative embodiments, thestopper 24 and the plunger 26 may initially be in contact with oneanother or coupled to one another, e.g., via a threaded coupling, suchthat they move together jointly from the start of movement of theplunger 26. Once the stopper 24 is in motion, it may continue to move inthe distal direction until it contacts a proximally-facing portion ofthe interior surface 15 of the wall of the drug storage container 20.This position of the stopper 24 may be referred to as the end-of-dose orend-of-delivery position, and may correspond to when delivery of thedrug 22 to the patient is complete or substantially complete.

In some embodiments, a volume of the drug 22 included in the reservoirof the drug storage container 20 may be equal to 1 mL, or equal toapproximately (e.g., ±10%) 1 mL, or equal to 2.5 mL, or equal toapproximately (e.g., ±10%) 2.5 mL, or equal to 3 mL, or equal toapproximately (e.g., ±10%) 3 mL, or less than or equal to approximately(e.g., ±10%) 1 mL, or less than or equal to approximately (e.g., ±10%) 2mL, or less than or equal to approximately (e.g., ±10%) 3 mL, or lessthan or equal to approximately (e.g., ±10%) 4 mL, or less thanapproximately (e.g., ±10%) 5 mL, or less than or equal to approximately(e.g., ±10%) 10 mL, or within a range between approximately (e.g., ±10%)1-10 mL, or within a range between approximately (e.g., ±10%) 1-5 mL, orwithin a range between approximately (e.g., ±10%) 1-4 mL, or within arange between approximately (e.g., ±10%) 1-3 mL, or within a rangebetween approximately (e.g., ±10%) 1-2.5 mL.

The delivery member 16 is connected or operable to be connected in fluidcommunication with the reservoir of the drug storage container 20. Adistal end of the delivery member 16 may define the insertion end 28 ofthe delivery member 16. The insertion end 28 may include a sharpened tipof other pointed geometry allowing the insertion end 28 to pierce thepatient's skin 5 and subcutaneous tissue during insertion of thedelivery member 16. The delivery member 16 may be hollow and have aninterior passageway. One or more openings may be formed in the insertionend 28 to allow drug to flow out of the delivery member 16 into thepatient.

In one embodiment, the drug storage container 20 may be a pre-filledsyringe and has a staked, hollow metal needle for the delivery member16. Here, the needle is fixed relative to the wall of the drug storagecontainer 20 and may be in permanent fluid communication with thereservoir of the drug storage container 20. In other embodiments, theneedle may be coupled to the drug storage container 20 via a Luer Lockor other suitable connection. In yet other embodiments, the drug storagecontainer 20 may be a needle-less cartridge, and, as such, initially maynot be in fluid communication with the delivery member 16. In suchembodiments, the drug storage container 20 may move toward a proximalend of the delivery member 16, or vice versa, during operation of thedrug delivery device 10 such that the proximal end of the deliverymember 16 penetrates through a septum covering an opening in the drugstorage container 20 thereby establishing fluid communication betweenthe reservoir of the drug storage container 20 and the delivery member16.

The drug storage container 20 may include a body portion 20 g with adistal end 20 e and a proximal end 20 f. The drug storage container 20may be fixed relative to the housing 12 such that the drug storagecontainer 20 does not move relative to the housing 12 once installed inthe housing 12. As such, the insertion end 28 of the delivery member 16extends permanently through the opening 14 in the housing 12 in thepre-delivery, delivery, and post-delivery states. For example, as shownin FIG. 2, the delivery member 16 extends beyond a distal end of thehousing 12 that defines the opening 14. However, in some configurations,such as the storage configuration shown in FIG. 2, the delivery member16 is covered/protected by the sterile barrier 21 and a guard member 32that surrounds the delivery member 16 and protects against or reducesthe likelihood of unintended or premature needle stick.

The container holder 31 may have a hollow and generally cylindrical ortubular shape centered about the longitudinal axis A, and the drugstorage container 20 may be disposed partially or entirely within thecontainer holder 31. A distal end of the container holder 31 may includean inwardly protruding flange 33 abutting against a shoulder portion 20a of the drug storage container 20, thereby preventing distal movementof the drug storage container 20 during actuation of the plunger 26.

In one embodiment, a container holder 31 secures and/or fixes theposition of the drug storage container 20 within the housing 12. Forexample, the container holder 31 may be configured to support the drugstorage container 20 with respect to the housing 12 proximal to at leasta portion of the distal end of the body portion of the drug storagecontainer 20 (including, for example, proximal to an entirety of thedistal end of the body portion of the drug storage container 20) suchthat a resultant force acting on the drug storage container 20 from theplunger biasing member 50 is at least substantially completely borne bythe distal end of the body portion of the drug storage container 20.

The term “body portion” of the drug storage container 20 as used hereinis the generally cylindrical portion of the drug storage container 20.For example, the body portion 20 g of the drug storage container 20shown in FIG. 4A extends from the distal side of the flange 20 c to theproximal side of the shoulder portion 20 a. As a more specific example,the body portion 20 g of the drug storage container 20 shown in FIG. 4Ahas a relatively constant inner diameter and/or a relatively constantouter diameter along its length. As shown in FIGS. 4A and 2, proximal tothe distal end 20 e of the body portion 20 g, the drug storage container20 defines the shoulder portion 20 a. The delivery member 16 extendsdistally from the distal end 20 e of the body portion 20 g of the drugstorage container 20. As a more specific example, the drug storagecontainer 20 further includes a neck portion 20 g positioned distally ofthe shoulder portion 20 a and configured to support the delivery member16 such as a staked needle.

The term “resultant force” refers to force the urging the drug storagecontainer 20 along the axis A upon and due to actuation of the plungerbiasing member 50 during and after the injection state. For example,when the plunger 26 is actuated and driven in the distal direction alongaxis A, it urges the stopper 24 in the distal direction. As a result ofthis direct contact between the plunger 26 and the stopper 24, as wellas frictional forces between the stopper 24 and the drug storagecontainer 20 and the forces required to urge the drug 22 through therelatively small-diameter delivery member 16, the drug storage container20 is urged in a distal direction even though the plunger 26 may notdirectly touch, abut, or engage the body portion of the drug storagecontainer 20. As a result, the drug storage container 20 may experiencea relatively high resultant force during the injection process, morespecifically during the actuation of the plunger 26.

The force concentration of the resultant force acting on the drugstorage container 20 during the plunger actuation is highest in theportion of the drug storage container 20 that is resisting distalmovement. For example, in the device shown in the figures, the forceconcentration is highest proximal to at least a portion of the distalend 20 e of the body portion 20 g of the drug storage container 20. As amore specific example, the force concentration is highest at theshoulder portion 20 a where the drug storage container 20 is supportedby the container holder 31. As an even more specific example, the forceconcentration is at least substantially completely borne by the shoulderportion 20 a of drug storage container 20. The term “substantiallycompletely” may mean greater than 50%, it may mean greater than 70%, itmay mean greater than 75%, it may mean greater than 80%, it may meangreater than 80%, it may mean greater than 85%, it may mean greater than90%, it may mean greater than 95%, it may mean greater than 98%, or anyother suitable number.

The force concentration of the resultant force acting on the drugstorage container 20 during the plunger actuation is preferably notsignificantly borne by the outwardly protruding flange 20 d of the drugstorage container 20. For example, because the force is substantiallycompletely borne by the distal portion 20 e of the body portion 20 g ofthe drug storage container 20, the force concentration in and near theoutwardly protruding flange 20 d is relatively low. As a more specificexample, the percentage of the resultant force acting on the entire drugstorage container 20 that is borne by the outwardly protruding flange 20d may be less than 20%, or it may be less than 15%, or it may be lessthan 10%, or it may be less than 5%, or it may be less than 3%, or itmay be less than 2%, or it may be less than 1%, or it may be about 0%.

As shown in FIGS. 2 and 4B, the container holder 31 includes a pluralityflanges 33 that each include an arcuate, sloped surface 33 a thatsubstantially matches the arcuate shape of the shoulder portion 20 a ofthe drug storage container 20. As a more specific example, when the drugstorage container 20 is inserted within the container holder 31, theflanges 33 cooperate to support the shoulder portion 20 a and limit thetravel of the drug storage container 20 in the distal direction. Theflanges 33 are separated from each other by a gap 33 b (FIG. 3b ) topermit flex of the flanges 33, as will be discussed below in moredetail. The container holder 31 shown in FIGS. 4A-4C includes fourflanges 33, but any suitable number of flanges may be utilized, as willbe discussed below with respect to another exemplary design shown inFIG. 4D.

The container holder 31 may have an open position 29 a (FIG. 4B) whereit is able to receive the drug storage container 20 during assembly anda closed position 29 b (FIGS. 4C) where it is able to support or atleast partially support the drug storage container 20. As a morespecific example, the container holder 31 includes a pair of arms 31 a,31 b extending axially from an annular ring 31 c such that the arms 31a, 31 b can flex away from or towards each other to move between theopen position 29 a and the closed position 29 b. The annular ring 31 cin the figures is positioned near the distal end of the container holder31 so that the proximal portions of the arms 31 a, 31 b are able toextend away from each other when the container holder 31 is in the openposition 29 a. The container holder 31 further includes matingconnectors 31 d, 31 e adjacent the top (proximal) portion of thecontainer holder 31 that are configured to snap-fit with each other whenthe container holder is in the closed position 29 b. As a more specificexample, when the mating connectors 31 d, 31 e are engaged with eachother, a frictional fit between the respective components holds thecontainer holder 31 in the closed position 29 b.

The container holder 31 shown in the figures also includes a pair ofinwardly-protruding flanges 31 f, 31 g positioned adjacent to theproximal end of the container holder 31. When the container holder 31 isin the open position 29 a, the inwardly-protruding flanges 31 f, 31 gare spaced apart from each other such that a radiallyoutwardly-protruding flange 20 b on the drug storage container 20 isable to be placed into the container holder 31 (via insertion in thedistal direction). In other words, when the container holder 31 is inthe open position 29 a the outwardly-protruding flange 20 b on the drugstorage container 20 is able to clear the gap between theinwardly-protruding flanges 31 f, 31 g. Once the drug storage container20 is fully inserted within the container holder 31 (e.g., such that theshoulder portion 20 a of the drug storage container 20 contacts theinwardly-protruding flanges 33) the container holder arms 31 a, 31 b areable to be moved into the closed position 29 b, in which theinwardly-protruding flanges 31 f, 31 g prevent the drug storagecontainer 20 from exiting the container holder 31 in the proximaldirection. In other words, once the drug storage container 20 isinserted into the container holder 31 and the drug storage container 20is in the closed position 29 b, the drug storage container 20 is heldwithin the container holder 31 by the inwardly protruding flanges 33near the distal end of the container holder 31 and by theinwardly-protruding flanges 31 f, 31 g near the proximal end of thecontainer holder 31.

As shown in FIGS. 4B and 4C, the container holder 31 includes opposingsurfaces 31 i, 31 h defining an opening 31 j for receiving the flange 20b of the drug storage container 20. For example, the container holder 31shown in the figures includes two distally-facing surfaces 31 i and twoproximally-facing surfaces 31 h that respectively cooperate to definetwo openings 31 j that each receive opposing portions of the flange 20b. The opposing surfaces 31 h, 31 i define the lower and upperboundaries for positioning of the flange 20 b when the drug storagecontainer 20 is positioned within the container holder 31 in the closedposition 29 b. This range from lower and upper boundaries may provideflexibility for drug storage containers 20 of varying lengths and/or fora range of tolerances for the length of the drug storage container 20.However, as discussed in more detail below, additional components of thedevice 10 may further secure the drug storage container 20 adjacent tothe flange 20 b when the drug storage container 20/container holder 31assembly is inside of the housing 12. The openings 31 j may also preventand/or restrict rotational movement of the drug storage container 20.For example, opposing rounded sections 20 c of the flange 20 b may eachextend at least partially through the openings 31 j and opposing linearsections 20 d of the flange 20 b may each abut side walls defining theopenings 31 j to prevent and/or restrict rotational movement between therespective components 20, 31.

As shown in FIG. 4B, the container holder 31 may include additionalmating connectors 31 k, 31 m, which are distally positioned from themating connectors 31 d, 31 e. The respective pairs of mating connectors31 d, 31 e; 31 k, 31 m may work together to create a snap fit betweenthe respective arms 31 a, 31 b of the container holder 31 to secure thesame in the closed position 29 b.

It may be desirable for the annular ring 31 c to be positioned generallyopposite (along axis A) of the mating connectors 31 d, 31 e tofacilitate opening and closing of the container holder arms 31 a, 31 b.For example, the distance between the annular ring 31 c and theinwardly-protruding flanges 31 f, 31 g may be proportional to theclearance gap between the inwardly-protruding flanges 31 f, 31 g whenthe container holder 31 is in the open position 29 a. Therefore, tomaximize the gap between the inwardly-protruding flanges 31 f, 31 g whenthe container holder 31 is in the open position 29 a, one can maximizethe distance between the annular ring 31 c and the inwardly-protrudingflanges 31 f, 31 g (e.g., the effective length of the arms 31 a, 31 b).Additionally, the thickness, height, and material properties of theannular ring 31 c may each affect the flex of the arms 31 a, 31 b and/orthe gap between the inwardly-protruding flanges 31 f, 31 g when thecontainer holder 31 is in the open position 29 a. As discussed above,the gap 33 b between the flanges may also facilitate and/or define theamount of flex of the arms 31 a, 31 b and/or the gap between theinwardly-protruding flanges 31 f, 31 g when the container holder 31 ismoved into the open position 29 a. For example, as the arms 31 a, 31 bflex outwardly, the flanges 33 may move inwardly.

The container holder 31 shown in the drawings may include an alignmentridge 31 n that abuts an inner surface of the housing 12, to radiallyalign the container holder 31 within the housing 12 during assembly andto prevent and/or restrict radial movement between the respectivecomponents 12, 31. As an example, the housing 12 may include a slot 12 aformed on the inner surface of the housing to receive the alignmentridge 31 n. The housing 12 may include multiple slots and the containerholder 31 may include multiple alignment ridges to radially align therespective components 12, 31. For example, the container holder 31 shownin the figures includes two alignment ridges 31 n and the housing 12includes two slots 12 a. The slots 12 a are spaced apart from each otherand sized such as to receive the respective alignment ridges 31 n whenthe container holder 31 is inserted into the housing 12. The slots 12 ashown in the figures are defined by a generally annular collar 12 dportion that is integral with the housing 12 (although the collarportion may alternatively be one or more components coupled or fixed tothe housing). The annular collar 12 d may not extend around the entireinner surface of the housing 12 and instead has cut-outs or gaps topermit portions of the guard member 32 to extend between respectiveportions of the annular collar 12 d. Alternatively, the annular collar12 d may be radially inwardly spaced apart from the inner surface of thehousing 12 in at least one or more locations to facilitate portions ofthe guard member to extend past the collar 12 d.

The annular collar 12 d may further define sloped surfaces 12 e onopposite sides of each of the lock slots 12 c to further assist withalignment between the container holder 31 and the housing 12.

The components shown in FIGS. 4A, 4B, and 4C includes an alignment ridge31 n that is positioned at the distal end of a support ridge 31 o. Forexample, the support ridge 310 has a smaller height (measuredperpendicularly to the outer surface of the container holder 31) thanthe alignment ridge 31 n such that only the alignment ridge 31 n isreceived within the alignment slot 12 a, rather than the support ridge31 o. Alternatively, the alignment ridge may extend substantially orcompletely along the axial length of the container holder 31, as will bediscussed below with respect to another exemplary design shown in FIG.4D.

The drug storage container 20 may be further or more securely coupledwith the container holder 31 (and as a result, to the housing 12) suchthat the drug storage container 20 and the container holder 31 areprevented from moving relative to the housing 12 during operation of thedrug delivery device 10. For example, as shown in FIGS. 4B and 4C, thecontainer holder 31 may include a plurality of lock ridges 33 c on theflanges 33 that form a friction-fit with portion(s) of the housing 12.As a more specific example and as shown in FIGS. 2 & 3B, the housing 12includes a plurality of lock slots 12 c that each receive respectivelock ridges 33 c of the container holder 31 to prevent and/or restrictrelative movement between the respective components 12, 31. As a morespecific example, the lock ridges 33 c each extend radially from theouter surfaces of the flanges 33. The container holder 31 may includeany suitable number of lock ridges 33 c, such as one, two, three, four,or more. The lock slots 12 c shown in the figures are defined by theannular collar 12 d, but they may be alternatively defined by anothercomponent. The lock slots 12 c are spaced apart from each other andsized such as to receive the respective lock ridges 33 c when the drugstorage container is positioned within the container holder 31. As amore specific example, the lock ridges 33 c snap into a friction-fitwith the lock slots 12 c such as to secure the container holder 31 and,as a result, the drug product container 20, within the housing 12. As aneven more specific example, when the lock ridges 33 c snap into the lockslots 12 c, the flanges 33 may inwardly compress slightly to form amore-secure fit between the container holder 31 and the drug productcontainer 20.

The container holder 31 inner surface may include a compressiblecomponent such as an elastomeric component that is positioned betweenthe inner surface of the container holder 31 and the drug productcontainer 20. As a more specific example, the elastomeric component maybe a rubber ring. Alternatively or additionally, the natural flex of theflanges 33 may function as the compressible component.

The lock ridges 33 c may give audible and/or tactile feedback to theuser or an assembly worker as they snap into the corresponding lockslots 12 c, thereby indicating to the assembler(s) that the respectivecomponents 12, 31 are positioned as desired. Additionally, therespective components may be sized and positioned such that the feedbackonly occurs when the drug product container 20 is also positioned asdesired. For example, if the drug product container 20 is positioned toofar in the distal direction with respect to the container holder 31,such that the main body of the drug product container 20 is aligned withthe flanges 33 instead of the shoulder portion 20 a being aligned withthe flanges 33, then the lock ridges 33 c may not be able to radiallycompress enough for the lock ridges 33 c to fit within the lock slots 12c. Conversely, if the drug product container 20 is not inserted farenough in the distal direction with respect to the container holder 31,such that the sterile barrier 21 is aligned with the flanges 33 insteadof the shoulder portion 20 a being aligned with the flanges 33, then thelock ridges 33 c will be able to radially compress inward to an extentthat the lock ridges 33 c will be able to slide radially inward of thelock slots 12 c or the lock ridges 33 c will enter the lock slots 12 cbut may not cause enough radially-outward force to generate the audibleand/or tactile feedback. While the audible and/or tactile feedback maybe advantageous during manual assembly of the container holder 31,assembly of the container holder 31 need not be performed manually andmay in some embodiments be performed partially or entirely bymanufacturing equipment.

The housing 12, container holder 31, and their respective components asdescribed above offer many advantages. For example, by securely couplingthe drug product container 20 with respect to the housing 12 via theshoulder portion 20 a (as opposed to the flange portion) the device 10may have reduced incidence of glass breakage or other damage. As a morespecific example, drug product containers such as syringes are oftenhave a shoulder portion that is stronger and/or able to handle higherforces than a flange portion. In other words, it may be advantageous forthe force concentration on the drug product container to be higher atthe shoulder than at the flange because the shoulder may be stronger andmore resistant to breakage than the flange.

As another potential advantage to this configuration, by securelycoupling the drug product container 20 with respect to the housing 12via a distal portion (e.g., the shoulder portion 20 a) the device 10 mayhave a more predictable, repeatable, and/or consistent injection depththan designs that secure the drug product container 20 via the flange(e.g. a “hanging” design). For example, the distance between theshoulder portion 20 a and the delivery member 16 for a syringe istypically more predictable and/or has a smaller manufacturing tolerancethan the distance between the flange 20 b and the delivery member 16because barrel length of a drug product container 20 can vary morewidely than the barrel shoulder length. Additionally or alternatively,the distance between the flange 20 b and the delivery member 16 includesany tolerances/variances in the distance between the shoulder portion 20a and the delivery member 16, so any tolerances/variances are “stacked.”

As shown in FIG. 4C, when the drug storage container 20 is inserted intothe container holder 31 and the drug storage container 20 is in theclosed position 29 b, a portion of the drug storage container 20 extendspast the distal end of the container holder 31. For example, the sterilebarrier 21 is positioned substantially or completely outside of thecontainer holder 31 to facilitate removal of the sterile barrier 21during use of the device 10, as is shown in FIGS. 4C and 4F and as willbe discussed in more detail below. Additionally, the delivery member 16extends past the distal end of the container holder 31 (as discussedabove).

FIG. 4D shows another exemplary container holder 131 that has somefeatures which are similar in function to those included in thecontainer holder 31, each of which is assigned with same referencenumeral except incremented by 100. For example, the container holder 131includes a pair of arms 131 a, 131 b; an annular ring 131 c connectingthe arms 131 a, 131 b; respective sets of mating connectors 131 d, 131e, 131 k, 131 m for selectively fixing the arms in a closed position 129b; a pair of inwardly-protruding flanges 131 f, 131 g; a pair ofopposing surfaces 131 h, 131 i for defining lower and upper limits oftravel for the drug storage container flange; and an opening 131 j forreceiving the drug storage container flange. The container holder 131also includes a plurality of flanges 133 positioned at a distal end ofthe container holder 131 and configured to support the drug storagecontainer. For example, the container holder 131 includes two flanges133, each of which includes an arcuate, sloped surface 133 a thatsubstantially matches the arcuate shape of a shoulder portion of thedrug storage container. The container holder 131 shown in FIG. 4D hastwo flanges 133 as opposed to the four flanges 33 shown in the containerholder 31 shown in FIGS. 4A-4C; therefore the flanges 133 eachpreferably have a greater circumference than the flanges 33. Thecontainer holder 131 also includes an alignment ridge 131 n that isreceived within an alignment slot 12 a formed in the inner surface ofthe housing 12 to properly align the container holder 131 within thehousing 12 during assembly and to prevent and/or restrict rotationalmovement between the respective components 12, 131. The alignment ridge131 n shown in FIG. 4D extends substantially completely along the axiallength of the container holder 131, in contrast to the alignment ridge31 n.

As with the container holder 31 shown in FIGS. 4B-4C, the containerholder 131 may include a plurality of lock ridges 133 c on the flanges133 that form a friction-fit with portion(s) of the housing 12. As amore specific example and as shown in FIGS. 4D and 4E, the housing 12includes a plurality of lock slots 12 c that each receive respectivelock ridges 133 c of the container holder 131 to prevent and/or restrictrelative movement between the respective components 12, 131. The lockridges 133 c may also give audible and/or tactile feedback to the useror an assembly worker as they snap into the corresponding lock slots 12c, thereby indicating to the assembler(s) that the respective components12, 131 are positioned as desired. Additionally, the container holder131 may provide the same or similar advantages as those described abovewith respect to the container holder 31.

In yet another exemplary design, the container holder may have a fixedstate, rather than having arms that open and closed. As a more specificexample, the container holder may have a proximal opening sufficientlysized to permit receipt of the syringe. The container holder may stillhave distally-located flanges for receiving and securing the shoulderportion of the syringe, particularly when the container holder iscoupled with the injector housing.

FIGS. 4F and 5A show distal (FIG. 4F) and proximal (FIG. 5A) portions ofthe drug product container 20 and its interactions with various othercomponents of the device 10. For example, FIG. 4F shows a partialcross-sectional view of a distal portion of the drug product container20 positioned within the container holder 31, with the shoulder portion20 a supported by the flanges 33. As another example, FIG. 5A shows across-sectional view of a proximal portion of the drug product container20 positioned within the container holder 31 such that the drug productcontainer flange 20 b is positioned between the opposing surfaces 31 h,31 i and within the opening 31 j. The drug product container 20 shown inFIG. 5A is further supported by the plunger guide 60, such as a flexiblearm 60 a of the plunger guide 60. As a more specific example, theflexible arm 60 a extends generally distally, and slightly radiallyinwardly, from a distal portion of the plunger guide 60 b. As an evenmore specific example, the plunger guide 60 shown in FIG. 5A includes adistal surface 60 b that abuts the inwardly-protruding flanges 31 f, 31g of the container holder 31; the flexible arm 60 a extends from thedistal surface 60 b in between the inwardly-protruding flanges 31 f, 31g.

The flexible arm 60 a may have a size, shape, and material type thatpromotes and/or permits flexure of the flexible arm 60 a. As a morespecific example, the flexible arm 60 a is preferably flexible in theradial direction, so that when the drug product container 20 and theplunger guide 60 are inserted within the housing, the flexible arm 60 ais aligned with the flange 20 b and applies at least a gentle radialforce (radially inwardly) on the drug product container 20. In thisconfiguration, the drug product container 20 is primarily supported atits distal portion (e.g., the shoulder portion 20 a) by the containerholder 31 and is also, at least secondarily, supported at its proximalportion (e.g., the flange portion 20 b) by the plunger guide 60. As amore specific example, the flexible arm 60 a may provide radial supportto the flange portion 20 b and prevent and/or resist transverse movementof the drug product container 20 with respect to the housing 12. Such aconfiguration may reduce or eliminate rattling noises from the device 10and/or may facilitate proper alignment of the drug product container 20during assembly. As another more specific example, the flexible arm 60 amay provide axial support (e.g., in the distal direction) to preventundesirable axial movement of the drug product container 20 with respectto the housing 12. The device 10 may have any suitable number offlexible arms 60 a, such as one, two, three, four, or more.

The container holder 31 may also include at least one support flange 31r that has a size, shape, and material type that promotes and/or permitsflexure thereof. As a more specific example, the support flange 31 r ispreferably flexible in the radial direction, so that when the drugproduct container 20 and the container holder 31 are inserted within thehousing, the support flange 31 r is aligned with the body portion 20 gof the drug product container and applies at least a gentle radial force(radially inwardly) on the drug product container 20. In thisconfiguration, the drug product container 20 is primarily supported atits distal portion (e.g., the shoulder portion 20 a) by the containerholder 31 and is also, at least secondarily, supported at a central orproximal region of the body portion 20 g by the container holder 31. Asa more specific example, the support flange 31 r may provide radialsupport to the drug product container 20 and prevent and/or resisttransverse movement of the drug product container 20 with respect to thehousing 12. Such a configuration may reduce or eliminate rattling noisesfrom the device 10 and/or may facilitate proper alignment of the drugproduct container 20 during assembly. As another more specific example,the support flange 31 r may but is not required to provide axial support(e.g., in the distal direction) to prevent undesirable axial movement ofthe drug product container 20 with respect to the housing 12. The device10 may have any suitable number of support flanges 31 r, such as one,two, three, four, or more. The container holder 31 shown in the figuresincludes four support flanges 31 r that are equally spaced about thecircumference thereof.

Although the flexible arm 60 a and/or the support flanges 31 r shown inthe figures provides at least some support for the drug storagecontainer 20, the container holder substantially completely supports thedrug storage container 20 with respect to the housing 12 by the distalend of the body portion 20 g of the drug storage container 20, asdiscussed above. As a more specific example, the flexible arm 60 aand/or the support flanges 31 r may provide little or no support alongthe longitudinal axis A and only provide support in a directiontransverse to Axis A. As an even more specific example, the containerholder 31 substantially completely supports the drug storage container20 with respect to the housing 12 by the distal end of the body portion20 g of the drug storage container 20 for forces along the Axis A, suchas forces experienced during the injection process.

As indicated above, the plunger guide 60 shown in FIG. 5A includes adistal surface 60 b that abuts the inwardly-protruding flanges 31 f, 31g of the container holder 31. This configuration may help reduce orprevent radial movement of the container holder 31 within the housing12. For example, as shown in FIG. 5A, the container holder includes anannular wall 31 p that cooperates with the inwardly-protruding flanges31 f, 31 g to define an annular seat for the distal surface 60 b of theplunger guide 60. The annular wall 31 p may center the plunger guide 60with respect to the container holder 31 and the drug product container20 so that the plunger 26 is likewise aligned with those components 31,20. The annular wall 31 p may also reduce or prevent radial movement ofthe plunger guide 60 with respect to the housing 12. This configurationmay also help reduce or prevent axial movement of the container holder31 within the housing 12. For example, as shown in FIG. 2, the plungerguide 60 extends from the rear end cap 23 to a mid-point of the device10 where it abuts the container holder 31. As a result, the containerholder 31 is restricted from moving axially upward in FIG. 2 (i.e.,proximally) by the plunger guide 60. Furthermore, the rear end cap 23may not be able to be installed unless the plunger guide 60 is properlyaxially and radially aligned with the container holder 31, such as ifthe distal surface 60 b is not abutting the inwardly-protruding flanges31 f, 31 g.

As shown in FIGS. 5B and 5C, the plunger guide 60 may have a hollow andgenerally cylindrical or tubular shape, and may be centered about thelongitudinal axis A. An outer diameter or other outer dimension of aproximal end of the plunger guide 60 may be larger than an outerdiameter or other outer dimension of a distal end of the plunger guide60. At least a portion of the distal end of the plunger guide 60 may bepositioned radially between the plunger 26 and the releaser member 52.As such, the plunger 26 may be disposed at least partially within thedistal end of the plunger guide 60, and the distal end of the plungerguide 60 may be disposed at least partially within the releaser member52, as illustrated in FIG. 2. Further features and functions of theplunger guide 60 are discussed below.

As shown in FIG. 2, the plunger guide 60 may be fixedly coupled with thehousing such that the plunger guide 60 is substantially and/or generallyimmovable relative to the housing 12. For example, and as shown in FIGS.1C and 5B, the plunger guide includes a lock tab 60 f that is sized,shaped, and aligned to be received within a lock key 12 f formed withinthe housing 12. As a more specific example, the plunger guide 60 andhousing 12 each include a pair of respective components 60 f, 12 f thatcooperate to prevent relative rotation between the plunger guide 60 andthe housing 12. Additionally or alternatively, annular ridges 60 gformed on an outer surface of the plunger guide 60 may form a frictionfit with the inner surface of the housing to resist or prevent rotationbetween the respective components 12, 60.

The plunger 26 (as best illustrated in FIGS. 2, 3A) may have a hollowand generally cylindrical or tubular shape. The plunger 26 may includean annular wall 39 with an outer surface 41 and an inner surface 43. Theinner surface 43 may define an interior space sized to receive a plungerbiasing member 50 therein. It is generally desirable to minimize athickness of the annular wall 39, to the extent possible and withoutcompromising the integrity of the plunger 26, so as to maximize an innerdiameter of the plunger 26. This allows a larger diameter plungerbiasing member 50 to fit within the interior space of the plunger 26,which, in turn, allows for a more powerful plunger biasing member 50. Asa more specific example, the thickness of the annular wall 39 may beless than 2 mm. As another more specific example, the thickness of theannular wall may be less than 1 mm. As another more specific example,the thickness of the annular wall may be less than 0.6 mm. As anothermore specific example, the thickness of the annular wall may be lessthan 0.3 mm. As another more specific example, the thickness of theannular wall may be less than 0.2 mm. As another more specific example,the thickness of the annular wall may be less than 0.1 mm. As anothermore specific example, the thickness of the annular wall may be lessthan 0.05 mm. The annular wall 39 may be made of any suitable material,such as metal or plastic. It may be advantageous for the annular wall 39to be made of metal, such as steel or aluminum, for the purposes ofminimizing the thickness of the annular wall 39. For example, a metalannular wall 39 may have sufficient axial strength and/or buckleresistance for use in the device if the annular wall 39 thickness isgreater than 0.05 mm. Conversely, a plastic annular wall 39 may havesufficient axial strength and/or buckle resistance for use in the deviceif the annular wall 39 thickness is greater than 1 mm.

The hollow rod 46 may additionally or alternatively facilitate and/orprovide more flexibility in spring design. For example, it may bedesirable or advantageous to use the device with different springsdepending on the characteristics of the drug and/or the desired drugdelivery profile. For example, a higher viscosity drug may require aspring with a higher spring rate and/or spring force and it thus may bedesirable or advantageous to have flexibility in physicalcharacteristics of the spring. As a more specific example, variousphysical characteristics of a spring may affect the spring rate, andthus the spring force, such as wire diameter of the spring (typicallyincreasing the wire diameter increases the spring rate), mean diameterof the spring (typically increasing the mean diameter decreases thespring rate), the number of spring coils (typically increasing thenumber of coils increases the spring rate), and the spring material.These physical characteristics may be adjusted to deliver differentspring rates, while also potentially adjusting the thickness of thehollow rod 46, to maintain a constant or relatively constant outerdiameter of the overall plunger 26 so as to keep constant the remainingparts of the device, such as the plunger guide 60 and the stopper 24.The hollow rod 46 may additionally or alternatively facilitate and/orprovide more longitudinal stability for the plunger biasing member 50,such as by preventing or reducing buckling or other transverse movement.

The plunger biasing member 50 shown in the figures may include thefollowing dimensions: 0.65 mm wire diameter, 5.40 mm outer diameter ofthe spring, and 80 to 86 number of coils (depending on pitch), but othersuitable spring characteristics may be utilized. The plunger biasingmember 50 shown in the figures may be formed of stainless steel strength2300 n/mm, but other suitable materials may be utilized. The hollow rod46 shown in the figures may include the following dimensions andmaterials: 63 mm length, 6 mm outer diameter, 0.20 mm wall thickness,and stainless steel strength 600 to 750 n/mm material, but othersuitable dimensions and materials may be utilized.

As described below in more detail, the plunger 26 may be configured toselectively rotate relative to the housing 12 and translate linearlyrelative to the housing 12 during operation of the drug delivery device10.

The plunger 26 may be constructed of multiple, interconnected pieces, oralternatively, have a one-piece construction. In the present embodiment,the plunger 26 is constructed of three separate and interconnectedstructures: a top ring 45 defining a proximal end of the plunger 26; abase 47 defining a distal end of the plunger 26; and a hollow rod 46positioned between and rigidly connecting the top ring 45 and the base47. The positions of the top ring 45, the hollow rod 46, and the base 47may be fixed relative to each other such that these components areimmoveable relative to each other. The top ring 45, the hollow rod 46,and the base 47 may each have an annular construction and be centeredabout the longitudinal axis A. The top ring 45 and the hollow rod 46 mayeach have a respective central opening extending from end to end of thecomponent to define an axial chamber; whereas, the base 47 may have acentral opening extending through the proximal end of the base 47 butwhich is closed off at the distal end of the base 47. The closed off endof the base 47 may define seat or abutment surface for the plungerbiasing member 50. In alternative embodiments, the central opening mayextend through the base 47 from end to end. In such alternativeembodiments, an inner diameter of the central opening of the base 47 maybe smaller than an outer diameter of the plunger biasing member 50 suchthat the base 47 retains a distal end of the plunger biasing member 50within the plunger 26. When the drive mechanism 30 is activated, thebase 47 may be the portion of the plunger 46 that comes into contactwith the stopper 24 to push the stopper 24 in the distal direction.

The top ring 45 may include one or more flanges or projections 48 whichextend radially outwardly from a central portion of the top ring 45.Each of the projections 48 may include a distally facing camming surface49. As described below in more detail, the distally facing cammingsurface 49 may interact with a counterpart camming surface on a plungerguide 60 in order to release the plunger biasing member 50. In someembodiments, the distally facing camming surface 49 may arranged atangle relative to, or is otherwise non-parallel to, an imaginary planeperpendicular to the longitudinal axis A.

In some embodiments, the top ring 45 and/or the base 47 may beconstructed of a different material than the hollow rod 46. In someembodiments, the top ring 45 and/or the base 47 made be constructed ofplastic whereas the hollow rod 46 may be constructed of metal. Soconfigured, the plastic material used for the top ring 45 may facilitatethe camming action described below by providing a relatively lowcoefficient of friction, the plastic material used for the base 47 mayhelp absorb or attenuate any shock or vibrations associated with base 47striking the stopper 24. The metal material used for the hollow rod 46may provide sufficient rigidity to avoid buckling under the biasingforce exerted by the plunger biasing member 50. In alternativeembodiments, the top ring 45, hollow rod 46, and/or base 47 may be madeof the same material, including, for example, metal or plastic. Incertain such embodiments, the top ring 45, hollow rod 46, and base 47may be integrally formed in one piece so as to define single, monolithicstructure.

The drug delivery device 10 may further include a guard mechanism forpreventing contact with the insertion end 28 of the delivery member 16when the drug delivery device 10 is not being used to administer aninjection. The guard mechanism may include a guard member 32 moveablydisposed at or near the distal end of the housing 12 adjacent to theopening 14. The guard member 32 may have a hollow and generallytubular-shaped or cylindrical portion 32 a centered about thelongitudinal axis A, and may have a pair of arms 32 b extendingproximally from the cylindrical portion 32 a. The guard member 32further includes a distal end 32 c that may generally include thecylindrical portion 32 a and a proximal end 32 d that may be defined bythe arms 32 b. The arms 32 b may be substantially or completely receivedwithin the housing 12 such that no part thereof extends from the housing12. The cylindrical portion 32 a may be at least partially and/orselectively received within the housing 12. For example, the guardmember 32 may be configured to move relative to the housing 12 such thatportions of the guard member 32 are received within the housing 12 insome stages/states and are extending from the housing 12 in otherstages/states, as is discussed below in more detail.

As one exemplary configuration, shown in FIGS. 2, 4E, and 6, the arms 32b of the guide member 32 are radially spaced apart from each other alonga circumference 32 g of the guard 32 such that the arms 32 b are able toslide between protruding sections of the annular collar 12 d formed onthe inner surface of the housing 12. For example, that the length of thearc between respective edges of the arms 32 b is at least slightlylarger than an arcuate length of a protruding section of the annularcollar 12 d so that the arms are able to axially slide between theprotruding sections of the annular collar 12 d without contacting thecollar.

As indicated above, the guard member 32 may be configured to moverelative to the housing 12 between an extended position wherein at leasta portion of the cylindrical portion 32 a of the guard member 32 extendsthrough the opening 14 in the housing 12 and a retracted positionwherein a shorter length of the cylindrical portion 32 a or no part ofthe cylindrical portion 32 a extends through the opening 14 in thehousing 12. In other words, in the extended position, a length X of thecylindrical portion 32 a extends from through the opening 14 in thehousing 12 and in the retracted position, a length Y of the cylindricalportion 32 a extends through the opening 14 in the housing 12, wherein Xis a value greater than Y. The length X may be any suitable number suchas 10 mm, 8 mm, 6 mm, 4 mm, 2 mm, 1 mm, or another value. The length Ymay be any suitable number that is less than X, such as 3 mm, 2 mm, 1mm, 0.5 mm, 0 mm, or another value. FIGS. 1C and 1D illustrate anexemplary pre-injected configuration (FIG. 1C) where the guard member 32is an extended position 32 e and the length of the exposed portion X ofthe guard member 32 may be approximately 5 mm to 11 mm and an injectionconfiguration (FIG. 1D) where the guard member 32 is in a retractedposition 32 f and the length of the exposed portion Y of the guardmember 32 is approximately 0 mm to 2 mm (such that the distal end 32 cof the guard member 32 is flush with the opening 14 of the housing 12).In one embodiment, the distance Y is greater than 0 (e.g. 1 mm) to helpensure the device 10 is able to be activated before the guard member isflush with the housing 12.

The guard member 32 may also be configured to move in the oppositedirection, namely from the retracted position to the extended position.When moving from the extended position to the retracted position, theguard member 32 may translate linearly in the proximal direction; andwhen moving from the retracted position to the extended position, theguard member 32 may translate linearly in the distal direction. In atleast the extended position, the guard member 32 may extend beyond andsurround the insertion end 28 of the delivery member 16. As a furtherillustration, FIGS. 1C and 2 show the guard member 32 in the extendedposition (and covered by the removable cap 19 in FIG. 2). As discussedabove, moving the guard member 32 from the extended position to theretracted position, e.g., by pressing the distal end of the guard member32 against the patient's skin at the injection site, may result in theinsertion end 28 of the delivery member 16 being inserted into thepatient's skin.

During the injection process the guard member 32 may remain stationarywith respect to the users skin 5 while the housing 12 and severalcomponents disposed therein are moving with respect to the guard member32 and the skin 5. Nonetheless, this disclosure refers to moving,retracting, translating, and depressing the guard member 32. Thesereferences and descriptions may be considered to refer to relativemovement between the guard member 32 and the housing 12, regardless ofwhich component (guard member 32 or housing 12) is moving with respectto the users skin 5.

The delivery device 10 may utilize inertial-driven design, rather than aspring-driven design, to insert the needle into the patient'ssubcutaneous tissue. As a more specific example, when the patientpresses the distal end of the guard member 32 against the patient's skinat the injection site, the delivery device 10 housing 12 may advancetoward the injection site. As the patient presses down a predetermineddistance or with a predetermined force, the delivery device 10 achievesa quick release to harness the energy stored in the patient's muscleswhile compressing the needle cover and its spring to a defined releasepoint. The release mechanism is designed such that the resulting needleinsertion speed exceeds the patient's reaction speed, and thecombination of this speed and the device's mass cause the needle toquickly and fully penetrate the skin to the subcutaneous depth. Comparedto known injectors, where the entire primary container is moved forwardwith respect to the housing, this embodiment prevents relative movementbetween the drug storage container 20 and the housing and therefore mayprovide a simplified, more robust design.

In alternative embodiments, the drug storage container 20 may bemoveably coupled to the housing 12 such that the drug storage container20 is able to move relative to the housing 12 during operation of thedrug delivery device 10. In certain such alternative embodiments, theinsertion end 28 of the delivery member 16 may be retracted within theopening 14 in the housing 12 in the pre-delivery state. Subsequently,during operation of the injection device 10, the insertion end 28 of thedelivery member 16 may be deployed through the opening 14 in the housing12 for insertion into the patient. This motion may, in some embodiments,be the result of the drug storage container 20 having been driven in thedistal direction relative to the housing 12.

In some embodiments, the guard member 32 may be rotationally fixed orrotationally restricted relative to the housing 12. Therefore, althoughthe guard member 32 may able to translate linearly relative to thehousing 12, the guard member 32 may be substantially or completelyprevented from rotating relative to the housing 12. As a more specificexample, the cylindrical portion 32 a of the guard member 32 may includea protrusion extending therefrom, for example a ridge 32 h, that alignswith a corresponding feature on the inner surface of the housing 12. Forexample, the inner surface of the housing, adjacent to the distal end ofthe housing 12 may include a slot, a pair of adjacent ridges, or anothercomponent or set of components that cooperate with the ridge 32 h tosubstantially or completely prevent rotation of the guard member 32.This arrangement may also help align the respective components 32, 12with each other during assembly.

The device 10 may further include an extender biasing member 35 and aguard extension 37. The guard extension 37 may be positioned proximal tothe guard member 32; and the extender biasing member 35 shown in thefigures is positioned proximal to the guard extension 37. The guardextension 37 may have a hollow and generally cylindrical or tubularshape centered about the longitudinal axis A. As a more specificexample, the guard extension 37 may include a generally cylindrical body37 a. The guard extension 37 may also include arms 37 b for receiving,supporting, and/or retaining a distal portion of the extender biasingmember 35. Furthermore, the guard extension 37 may be moveable in alinear direction along the longitudinal axis A relative to the housing12. In the present embodiment, the guard extension 37 is a separatestructure from the guard member 32. However, in alternative embodiments,the guard extension 37 and the guard member 32 may be integrally formedin one piece to define a single, monolithic structure. In suchalternative embodiments, the proximal end of the guard member 32 maycorrespond to the guard extension 37.

Similar to the guard member 32, the guard extension 37 may berotationally fixed relative to the housing 12. Therefore, although theguard extension 37 may able to translate linearly relative to thehousing 12, the guard extension 37 may be prevented from rotatingrelative to the housing 12. To achieve this effect, in some embodimentsthe guard extension 37 may cooperate with the plunger guide 60 torestrict or prevent rotation between the respective components 37, 60.As a result, and because the plunger guide 60 is fixedly connected withthe housing 12, the guard extension 37 may be rotationally fixed to thehousing 12 through the plunger guide 60. For example, the plunger guide60 may include a longitudinal ridge 60 c near a distal portion of theplunger guide 60. The ridge may be received within a longitudinalchannel on the inside surface of the guard extension 37 and/or a pair orcorresponding features that cooperate to receive the ridge 60 c. Inalternative embodiments, the ridge-and-slot arrangement may be reversed,such that the guard extension 37 has one or more radially inwardlyextending ridges and plunger guide has one or more slots or otherrecesses to matingly or snugly receive the one or more ridges. As yetanother alternative, the guard extension 37 may include an anti-rotationfeature that mates with a corresponding feature on the inner surface ofthe housing 12.

The guard extension 37 and/or the releaser member 52 may have axialtravel limits that limit the distance they are able to travel in thedistal direction. For example, as illustrated in FIG. 6C, the plungerguide 60 may include and axial ridge 60 c formed on the outer surfaceand positioned adjacent to a distal portion of the plunger guide 60. Adistally facing surface 52 j of the releaser member 52 may abut aproximally facing surface 60 d defined by the axial ridge 60 c, therebydefining the distal-most point of travel for the releaser member 52. Thereleaser member 52 also may include the locking flange 52 a that in turnlimits the distal travel of the guard extension 37. For example, thelocking ridge 52 a may abut an annular collar 37 d of the guardextension 37 to define the distal-most point of travel for the guardextension 37. The axial ridge 60 c and the locking ridge 52 a shown inthe figures do not necessarily limit travel of the releaser member 52and the guard extension 37 in the proximal direction, just the distaldirection.

As is best illustrated in FIG. 2, the extender biasing member 35 ispositioned between and in contact with the guard extension 37 and areleaser member 52. The extender biasing member 35 may be configured tobias or urge the guard extension 37 in the distal direction and/or biasor urge the releaser member 52 in the proximal direction. In the device10 shown in FIG. 2, which is in the pre-delivery or storage state, theextender biasing member 35 is initially in an energized state (e.g.,compressed). In other words, when the device 10 is in the pre-deliverystate, as shown in FIG. 2, the extender biasing member 35 exerts adistal direction (downward) biasing force on the guard extension 37 anda proximal direction (upward) biasing force on the releaser member 52.

During operation of the device, a user may cause the guard member 32 totranslate (with respect to the housing 12) in the proximal direction bypressing the guard member 32 against the injection site. In doing so,the guard member 32 will move towards the guard extension 37 and closethe gap 37 g therebetween (FIG. 2). Once the gap 37 g is eliminated, theguard member 32 and the guard extension 37 move jointly in the proximaldirection until, for example, the guard member 32 reaches the retractedposition 32 f. When the injection is complete and the drug deliverydevice 10 is lifted off of the injection site, the extender biasingmember 35 may urge the guard extension 37 so that the guard extension 37and the guard member 32 move jointly in the distal direction. Thismotion (and/or a biasing force from lock ring biasing member 51) returnsthe guard member 32 to the extended position 32 e, which has the effectof covering the insertion end 28 of the delivery member 16. In someembodiments, the extender biasing member 35 may include a compressionspring (e.g., a helical compression spring). Furthermore, in embodimentswhere the plunger biasing member 50 also includes a compression spring,the extender biasing member 35 may disposed around and/or have a largerdiameter than the plunger biasing member 50.

However, in some alternative embodiments, the extender biasing member 35may be in non-energized (natural) state when the device is in apre-delivery state. In these embodiments, the biasing member 35 maybecome compressed or energized upon deflection of the guard member 32 inthe proximal direction.

After drug delivery is complete and the guard member 32 has beenre-deployed to the extended position, it may be desirable to lock theguard member 32 in the extended position to prevent subsequent usercontact with the insertion end 28 of the delivery member 16 and/or toprevent re-use of the drug delivery device 10. Pursuant to these ends,some embodiments of the drug delivery device 10 may include a lock ring40 configured to selectively rotate, depending on the axial position ofthe guard member 32, in order to lock the guard member 32 in theextended position once the guard member 32 has moved from the retractedposition to the extended position, as will be discussed in more detailbelow.

As discussed above, the plunger biasing member 50 may be disposed atleast partially within the plunger 26, and may have a distal endabutting against a proximally facing inner surface of the plunger 26and/or may be fixedly attached to an inner surface of the plunger 26. Sothat the plunger biasing member 50 may be received within the plunger26, an outer diameter or other dimension of the plunger biasing member50 may be equal to or less than an inner diameter of the top ring 45and/or equal to or less than an inner diameter of the hollow rod 46. Insome embodiments, the distal end of the plunger biasing member 50 mayabut against a proximally facing inner surface of the base 47 of theplunger 26. Furthermore, as best illustrated in FIGS. 2 and 3A, aproximal end 50 a of the plunger biasing member 50 may abut against adistally facing surface 38 a of the plunger biasing member seat 38. Theplunger biasing member seat 38 may be fixedly attached to the rearhousing 27 such that the plunger biasing member seat 38 provides astationary surface for the plunger biasing member 50 to push off of. Forexample, as shown in FIGS. 3A and 5B, the plunger seat 38 may includeflanges 38 b that are received within openings 60 h formed in a proximalportion of the plunger guide, thereby fixedly coupling the plunger seatto the plunger guide 60. So configured, the plunger biasing member 50,when released from the energized state, may expand in length with distalend of the plunger biasing member 50 moving in the distal direction awayfrom the stationary proximal end of the plunger biasing member 50. Thismotion may push the plunger 26 is the distal direction, which, in turn,may push the stopper 24 in the distal direction to expel the drug 22from the drug storage container 20 into the delivery member 16 andthereafter into the patient. However, in the embodiment shown in thefigures, neither the release of the plunger biasing member 50 nor anyother biasing members cause the delivery member 16 to drive downwardwith respect to the housing 12. On the contrary, the drug productcontainer 20, and a as a result the delivery member 16, is substantiallyor completely fixedly coupled with respect to the housing 12. Rather,the delivery member 16 is driven into the patient's skin 5 by inertialforce generated by a downward force by the patient (or a health careprovider or other person administering the dose).

Referring to FIGS. 7A and 7B, of the releaser member 52 may have ahollow and generally cylindrical or tubular shape, and may be centeredabout the longitudinal axis A. As illustrated in FIG. 2, the releasermember 52 may be radially positioned between the plunger guide 60 andthe guard extension 37. As also illustrated in FIG. 2, the releasermember 52 is also radially positioned between the guard extension 37 andthe plunger guide 60. Furthermore, the extender biasing member 35 may beaxially positioned between the releaser member 52 and the guardextension 37 and may be radially arranged around the releaser member 52.Generally, the releaser member 52 is configured to: (1) operably couplethe guard member 32 and the plunger 26 in an activation sequence and (2)generate an audible signal indicating the end of drug delivery. Soconfigured, the releaser member 52 is exploited to perform two separatefunctions, and thus reduces the number of moving parts required by thedrug delivery device 10.

The channel surfaces 52 b are each configured to receive the projections48 of the top ring 45 and permit axial movement of the plunger 26 withrespect to the releaser member 52 but to resist or prevent rotationalmovement between the plunger 26 and the releaser member 52. As shown inthe figures, although the channel surface 52 extends adjacent to theinner surface of the releaser member 52, the channel surface 52 does nothave an arcuate shape and instead has a generally squared-off shape (asbest illustrated in FIGS. 7B and 10A).

The releaser member 52 includes a channel surface 52 b that extendsproximally past the proximal-most (e.g., top) surface of the tubularbody of the releaser member 52. For example, the releaser member 52includes a proximally facing contact surface 52 d for end-of-dosenotification, which will be described in more detail below, and thechannel surfaces 52 b each extend past the contact surface 52 so as toprovide a continuous path with respect for the top ring 45 while alsopermitting a sufficient gap between the proximally facing contactsurface 52 d and the corresponding surface involved in end-of-dosenotification.

The releaser member 52 may be configured to rotate relative to thehousing 12 and/or translate linearly relative to the housing 12,depending on the stage of operation of the drug delivery device 10.Initial rotation of the releaser member 52 associated with activationmay be powered by the plunger biasing member 50 and/or the extenderbiasing member 35; whereas later rotation of the releaser member 52associated with generation of the end-of-dose signal may be poweredsolely by the extender biasing member 35. Any linear translation of thereleaser member 52 without rotation may be powered solely by theextender biasing member 35. In some embodiments, the releaser member 52may translate linearly only in the proximal direction; however,alternative embodiments may permit linear translation of the releasermember 52 in both the proximal and distal directions.

Having described the general configuration of the drug delivery device10, a method of using the drug delivery device 10 to perform aninjection will now be described with reference to FIGS. 9A-12C. As apreliminary step, the user may remove the drug delivery device 10 fromany secondary packaging, such as a plastic bag and/or cardboard box.Also, as a preliminary step, the user may prepare the injection site,e.g., by rubbing the patient's skin with an alcohol wipe. Next, the usermay pull and detach the removable cap 19 from the front housing 25. As aresult of this motion, the gripper 13 may pull and detach the sterilebarrier 21 from the drug storage container 20. This may uncover theinsertion end 28 of the delivery member 16. Nevertheless, the insertionend 28 of the delivery member 16 will remain surrounded by the guardmember 32 at this stage because the guard member 32 is arranged in theextended position. Next, the user may position the drug delivery device10 over the injection site and then push the distal end of the guardmember 32 against the injection site. The force applied by the user willovercome the biasing force of the extender biasing member 35 and thebiasing force of the lock ring biasing member 51, thereby causing theguard member 32 to retract into the opening 14 moving from the extendedposition to the retracted position in the proximal direction. Thedelivery member 16 remains stationary relative to the housing 12 duringthe retracting movement of the guard member 32.

Several of the device components include various features, surfaces, andopenings for interacting with and controlling the release movement ofthe plunger 26 (e.g. the injection sequence). Generally, the injectionsequence begins with retraction/axial movement of the guard member 32 inthe proximal direction (upward in FIG. 2), which causes axial movementof the guard extension 37, which unlocks the releaser member 52. Oncethe releaser member 52 is unlocked (e.g. first stage of travel), theplunger 26 and the plunger biasing member 50 urge the releaser member 52to rotate clockwise and permit axial movement of the plunger 26 (in thedistal direction, downward in FIG. 2). The plunger then urges thestopper 24 in the distal direction, thereby urging the drug 22 from thedrug product container 20 and out of the delivery member 16. Once theplunger has reached a certain point along the axial length of thedevice, movement of the releaser member 52 is further unlocked (e.g.second stage of travel) and the releaser travels in the proximaldirection (upward in FIG. 2) and into contact with the plunger guide 60,thereby generating an end-of-dose indication (such as an audible click).The injection sequence will now be described in more detail.

The pre-injection stage is shown in FIGS. 2, 9A, 10, and 11A. Movementof the guard member 32 from the extended position to the retractedposition may cause several actions to occur. Because the delivery member16 remains stationary relative to the housing 12 during retraction ofthe guard member 32, the insertion end 28 of the delivery member 16 iscaused to extend through an opening in the distal end of the guardmember 32, thereby piercing the patient's skin at the injection site andpenetrating into the patient's subcutaneous tissue. In addition,retraction of the guard member 32 may also activate the drive mechanism30 to expel the drug 22 from the drug storage container 20, as describedbelow in more detail.

In the pre-delivery state prior to retraction of the needle guard 32,the plunger 26 and the releaser member 52 each may be arranged in arespective initial rotational position, as illustrated in FIGS. 9A, 10,and 11A. The plunger biasing member 50 may be in an energized state. Asa consequence, the plunger biasing member 50 may exert a distallydirected biasing force on the plunger 26 which urges the distally facingcamming surface 49 against the proximally facing camming surface 60 j. Aresulting camming action may urge the plunger 26 to rotate in theclockwise direction. Despite these biasing force(s), neither thereleaser member 52 nor the plunger 26 rotates in the pre-delivery state.This is because the releaser member 52 and the plunger are rotationallyfixed in the pre-injection state. Accordingly, the releaser member 52,the plunger guide 60, the guard extension 37, and the housing 12 work inconjunction with one another to retain the plunger biasing member 50 inthe energized state prior to retraction of the guard member 32, as isnow described in more detail.

As best shown in FIG. 2, as the guard member 32 travels in the proximaldirection (upward in FIG. 2), the proximal end 32 d of the guard member32 contacts a distally-facing surface of the guard extension 37 andurges the guard extension in the proximal direction. As shown in FIGS.6B and 7A the inner surface of the guard extension 37 annular wallincludes a locking flange 37 c and the outer annular surface of thereleaser member 52 a corresponding locking flange 52 a. When the deviceis in the pre-injection stage, as shown in FIGS. 2, 9A, 10A, and 11A,the guard extension 37 locking flange 37 c engages the releaser member52 locking flange 52 a, thereby rotationally locking the releaser member52 (as best illustrated in FIG. 11A). At this point in the sequence, thedistally facing camming surface 49 of top ring 45 of the plunger 26 isabutting against a proximally facing camming surface 60 j of the plungerguide 60 such that the plunger 26 is restrained from axial travel due tothis interaction (best illustrated in FIGS. 9A and 10A). The distallyfacing camming surface 49 and/or the proximally facing camming surface60 j includes a sloped surface to promote relative movement of theplunger 26 top ring 45 in the direction of arrow 60 k in FIGS. 9A and10A (clockwise). For example, the distally facing camming surface 49 hasa slope 60 m of approximately 10 degrees (best illustrates in FIGS. 9Band 9C) but may have any suitable slope such as 9 to 11 degrees, 8 to 12degrees, 7 to 13 degrees, 6 to 14 degrees, 5 to 15 degrees, 4 to 16degrees, or any other suitable slope. Additionally or alternatively, thedistally facing camming surface 49 of top ring 45 may have a slope 49 aof approximately 10 degrees but may have any suitable slope such as 9 to11 degrees, 8 to 12 degrees, 7 to 13 degrees, 6 to 14 degrees, 5 to 15degrees, 4 to 16 degrees, or any other suitable slope. The slope(s) onone or more of the respective surfaces 60 j, 49 causes the axial forcefrom the plunger biasing member 50 to generate a force in the transversedirection, thereby urging the plunger 26 top ring 45 in the clockwisedirection 60 k. However, as discussed above, the releaser member 52resists or prevents rotational movement between the releaser member 52and the plunger while the top ring 45 is positioned within and/orcontacting the channel surface 52 b. As a result, as long as the guardextension 37 is rotationally locking the releaser member 52 (as shown inFIGS. 2, 9A, 10A, and 11A), then the top ring 45 will remainrotationally locked by the channel surface 52 b and axially locked bythe proximally facing camming surface 60 j.

The unlocking stage is shown in FIG. 11B, where the guard extension 37translates in the proximal direction until the guard extension 37locking flange 37 c no longer engages the releaser member 52 lockingflange 52 a and the releaser is no longer rotationally locked. At thisstage in the injection sequence, two things happen simultaneously ornear simultaneously: (1) the guard biasing member 35 urges the releasermember 52 in the clockwise direction (shown in FIG. 9B) and upward dueto a camming surface on one or both of the inner surface of the releasermember 52 (generally aligned with numeral 52 c labeled in FIGS. 9C and7B, but on the inner surface of the releaser member 52 rather than theouter surface as indicated by 52 c) or the outer surface of the plungerguide 60 (such as rib 60 n, FIG. 5B) that translates the axial forcefrom the guard biasing member 35 into a transverse (clockwise) force andcauses the releaser member 52 to rotate clockwise and move upward(proximally) and (2) the plunger biasing member 50 urges the top ring 45in the clockwise direction and downward (distally) due to the cammingaction between surfaces 49, 60 j of the plunger 26 and the plunger guide60 thereby causing the plunger 26 to move clockwise and slightlydownward along ramped surface 60 j. In other words, the releaser member52 and the plunger 26 top ring 45 are both rotating clockwise at thesame time or substantially the same time, due to forces from respectivebiasing members 35, 50. This sliding motion between surfaces 49, 60 j ofthe plunger 26 and the plunger guide 60 results in rotation, as well aslinear translation (not unlike a spiral pathway). Accordingly, theplunger guide 60 may function as a cam and the plunger rod 26 the camfollower.

The unlocked stage is shown in FIGS. 9B, 10B, and 11C. In this stage,the distally facing camming surface 49 of the top ring 45 has clearedthe proximally facing camming surface 60 j of the plunger guide 60 suchthat the top ring 45 (and thus the plunger 26) is no longer axiallyrestrained by the plunger guide 60. As a result, the plunger biasingmember 50 urges the plunger 26 axially in the distal direction.

The downward stroke stage is shown in FIGS. 9C, 10C, and 12A. At thispoint in FIGS. 9C, 10C, and 12A, the top ring 45 is still visible nearthe proximal portion of the plunger guide 60, but it will quickly travelalong a longitudinal slot 86 formed in the plunger guide 60 and thechannel surface 52 b. During this stage, the plunger 26 top ring 45 istraveling along both the channel surface 52 b of the releaser member 52and the longitudinal slot 86 of the plunger guide 60, thereby preventingrotation between any of the three components (26, 52, 60). As a morespecific example, because the plunger guide 60 is rotationally fixedwith respect to the housing 12, while the top ring 45 is positionedwithin both the channel surface 52 b and the longitudinal slot 86, thereleaser member 52 is unable to rotate. Also during this stage, as theplunger 26 travels distally, the gap 18 between the base 47 of theplunger 26 and the stopper 24 shrinks and the base 47 contacts thestopper 24. The device 10 is designed such that plunger 26 is travelingwith a force sufficient to drive the stopper 24 in the distal directionand urge the drug 22 from the delivery member 16. At the same time, thedevice 10 is also designed such as to reduce or eliminate the likelihoodof glass breakage, undesirable forces acting on the patient, and/orundesirable impact vibration or sound due to interaction between thebase 47 and the stopper 24. For example, the plunger biasing member 50design parameters may be designed to meet these two sets of designgoals. As another example, a damping component may be positioned betweenthe base 47 and the stopper 24 or in another location in the device 10to dampen the forces between the base 47 and the stopper 24. Forexample, the base 47 may include an elastomeric component, section, orother damping feature. Additionally or alternatively, the stopper 24 maybe formed of an elastomeric material that includes inherent dampingproperties. Additionally or alternatively, the stopper 24 may include anadditional elastomeric component, section, or other damping feature.

In some embodiments, the camming action between the distally facingcamming surface 49 on the projection 48 and the proximally facingcamming surface 60 j of the plunger guide 60 may provide a dampingeffect. More particularly, a sliding friction between these two surfacesmay be selected to slow initial expansion of the plunger biasing member50. As a consequence, the velocity of the plunger 26 may be reducedduring the initial expansion of the plunger biasing member 50, ascompared to free uninhibited expansion of the plunger biasing member 50.The reduced velocity of the plunger 26 may cause the plunger 26 tostrike the stopper 24 with less force, which reduces the chances ofstructural damage to the drug storage container 20 and/or facilitates amore comfortable injection for the user.

The end-of-dose stage is shown in FIGS. 12B and 12C. As discussed above,during the downward stroke stage, while the top ring 45 is positionedwithin the channel surface 52 b and the longitudinal slot 86, thereleaser member 52 is unable to rotate with respect to the plunger guide60. However, in the end-of-dose initiation stage shown in FIG. 12B, thetop ring 45 in some embodiments may clear the distal end of the releasermember 52 and no longer restricts or prevents rotation of the releasermember 52. As a more specific example, as shown in the bottom portion ofFIG. 12B, as the top ring 45 exits the channel surface 52 b and/or adistal surface 52 d of the releaser, the releaser member 52 is no longerrotationally constrained by the top ring 45 and the releaser member 52is urged upward by the guard biasing member 35. As a result of theupward force of the guard biasing member 35 and camming surfaces, thereleaser member 52 rotates clockwise while it moves upward in a spirallike path and a proximal facing surface 52 d of the releaser member 52contacts a distal facing surface 60 p of the plunger guide 60, therebymaking an audible click sound. As a more specific example, FIG. 12Bshows a gap 90 between the respective surfaces 52 d, 60 p, but that gap90 is then eliminated when the releaser member 52 travels proximally, asshown in FIG. 12C. The length of the channel surface 52 b and plunger 26may be designed so that the top ring 45 exits the channel surface 52 bas the stopper 24 reaches a desired point of travel within the drugstorage container 20, such as its end of travel near the distal end ofthe drug storage container 20.

As a more specific example of the camming surface arrangement betweenthe releaser member 52 and the plunger guide 60, and as discussed above,the rib 60 n of the plunger guide 60 is aligned with the inner surfaceof the releaser member 52 that is indicated by 52 c in FIG. 7A and inFIG. 7B (but on the inner surface rather than the outer surface asindicated by 52 c). The rib 60 n has a sloped surface to help facilitateand/or promote relative rotation between the components 52, 60. Morespecifically, the urging force of the guard biasing member 35, combinedwith the sloped surface of the rib 60 n, creates a rotational force(e.g., torque) and causes the releaser member 52 to rotate with respectto the plunger guide 60. During the first stage of releaser member 52rotation (e.g., the unlocking stage shown in FIG. 11B), the rib 60 ntravels along a first section of the inner camming surface 52 c of thereleaser member 52, such as the first section 52 f shown in FIG. 7B.During the second stage of releaser member 52 rotation (e.g., theend-of-dose stage shown in FIGS. 12B and 12C), the rib 60 n travelsalong a second section of the inner camming surface 52 c of the releasermember 52 such as the second section 52 g shown in FIG. 7B. As isvisible in FIG. 7B, the second section 52 g includes a pocket 52 h thatis able to receive the rib 60 n and permit the releaser member 52 toquickly move proximally towards the plunger guide 60 and cause theend-of-dose audible click. In summary, during the end-of-dose stage, thetop ring 45 clears the channel surface 52 b of the releaser member 52and the guard biasing member 35 and the rib 60 n cause the releasermember 52 to rotate and move upwards, ending with a quick upward(proximal) movement of the releaser member 52 into contact with theplunger guide 60 as the rib 60 n moves into the pocket 52 h.

Once the patient and/or health care provider hears the audible sound,he/she/they may be notified that the dose is complete. In someembodiments, the user may be informed of the significance of the audiblesignal by way of instructions provided with the drug delivery device 10.In some embodiments, these instructions may take the form of anInstructions for Use (IFU) pamphlet packaged together with the drugdelivery device 10. In some embodiments, the user may obtain additionalconfirmation that drug delivery is complete by watching movement of thestopper 24 and/or plunger 26 through the window 17. In some embodiments,the audible signal may be accompanied by a vibration or other tactilefeedback produced as a result of the releaser member 52 striking theplunger guide 60. The audible notification may be in the form of a clickor slap sound, or any other suitable audible signal that is perceptibleto the user. The audible signal may be generated simultaneously, orsubstantially simultaneously, with the stopper 24 reaching theend-of-dose position.

As described above, in addition to its retaining function, the releasermember 52 may also be used to generate an audible signal indicating tothe user that drug delivery or dosing is complete. This dual-functionrole may reduce part quantity and/or design complexity. Alternatively,the releaser member 52 does not need to have this indicator function. Inalternative embodiments, the indicator may be defined by a structurethat is separate from but rigidly attached to the releaser member 52.

While the foregoing descriptions may utilize the extender biasing member35 to provide the actuation energy needed generating the end-of-dosesignal, alternative embodiments may utilize a biasing member that isseparate from extender biasing member 35 for this purpose. In certainsuch embodiments, this additional biasing member may have a distal endfixed relative to the housing 12 and a proximal end abutting against adistally facing surface of the releaser member 52. As such, the biasingmember may push off of the housing 12 to exert a biasing force in theproximal direction against the releaser member 52. Furthermore, thisbiasing member may operate independently of the plunger biasing member50 and the extender biasing member 35.

In any case, once the user receives some assurance that drug delivery iscomplete, the user may then lift the drug delivery deice 10 off of theinjection site. With nothing to resist it, the extender biasing member35 may push the guard member 32 from the retracted position to theextended position to cover the insertion end 28 of the delivery member16. In some embodiments, this movement of the guard member 32 may causethe lock ring 40 to rotate to a position where it prevents subsequentretraction of the guard member 32.

For example, as discussed above, in some embodiments of the drugdelivery device 10 may include a lock ring 40 configured to lock theguard member 32 in the extended position once the guard member 32 hasmoved from the retracted position to the extended position In thepresent embodiment, the lock ring 40 is centered and rotates about thelongitudinal axis A. As illustrated in FIG. 2, a proximal end of thelock ring 40 may be in contact with the a portion of the housing 12 andthe distal end of the lock ring 40 may be disposed at least partiallywithin the guard member 32. The lock ring biasing member 51 may bepositioned in the axial direction between a distally facing surface ofthe lock ring 40 and a proximally facing surface of the guard member 32.The lock ring biasing member 51 may initially be in a compressed orenergized state such that it biases the lock ring 40 and the guardmember 32 away from each other. As such, the lock ring biasing member 51may exert a biasing force urging the guard member 32 toward the extendedposition, as well as exert a biasing force urging the proximal end ofthe lock ring 40 against a portion of the housing 12, such as theannular collar 12 d. In some embodiments, the lock ring biasing member51 may include a compression spring (e.g., a helical compressionspring).

The lock ring 40 may also serve to provide an initial resistance tomovement of the guard member 32. As discussed above, the device 10 maybe inserted into the patient by utilizing, harness, or otherwise takingadvantage of inertial forces. The lock ring 40 and/or other componentsmay provide an initial resistance to movement of the guard member 32 tobuild-up the user inputted force, as is discussed in more detail below.

FIG. 13 shows a perspective view of the lock ring 40. In the exampleshown in FIG. 13, the lock ring 40 includes a camming surface 40 a thatis non-parallel to the axis A and configured to convert translationalmovement of the shield guard 32 into rotational movement of the lockring 40. As a more specific example, the camming surface 40 a shown inFIG. 13 is at an angle 40 d to the axis A of approximately −30 degrees.Any suitable angle may be utilized, such as −10 to −80 degrees, −20 to−70 degrees, −20 to −60 degrees, −20 to −50 degrees, −20 to −40 degrees,−25 to −35 degrees, or any other suitable angle. The angle 40 d may be apositive number as well (such that the angled surface is flipped aroundthe axis A), but such as configuration would cause the lock ring 40 torotate in the opposite direction. In such a case, any suitable angle maybe utilized, such as 10 to 80 degrees, 20 to 70 degrees, 20 to 60degrees, 20 to 50 degrees, 20 to 40 degrees, 25 to 35 degrees, or anyother suitable angle.

In the example shown in FIG. 13, the lock ring 40 includes a locking arm40 b that may be a generally cantilevered arm extending (along acircumference of the lock ring 40) from a body portion of the lock ring40. The locking arm 40 b may include a ridge 40 c extending transverselyto the body portion of the lock ring 40 (i.e. outwardly and non-parallelto the axis A).

FIG. 14 shows the lock ring 40 along with other various components ofthe device in a pre-deflection stage (e.g., before the guard member 32has deflected axially in the proximal direction). For example, FIG. 14shows a distal portion of the housing 12 that is in partialcross-sectional view for illustrative purposes, the guard member 32 intranslucent form and partially cut-away for illustrative purposes, thelock ring 40, and a portion of the housing inner collar 12 d. The guardmember 32 includes a plurality of ribs formed on the annular innersurface thereof. These ribs are shown in FIG. 14, but portions of theannular surface itself have been cut away for illustrative purposes.Similarly, although portions of the housing 12 have been cut away forillustrative purposes, the annular collar 12 d formed on the innersurface of the housing 12 is visible in FIG. 14. When the device 10 isin the pre-deflection stage (as shown in FIG. 14), the ridge 40 c isadjacent to an inertial rib 32 k formed on the inner annular surface ofthe guard member 32. As a more specific example, when the device 10 isin the pre-deflection stage, the ridge 40 c is disposed to the left ofthe inertial rib 32 k such that the lock ring 40 generally resistsrotation (and thereby resists axial deflection of the guard member 32)until the ridge 40 c is able to move past the inertial rib 32 k (i.e. toclear the inertial rib 32 k). This arrangement is discussed in moredetail below.

FIGS. 15A and 15B show views from different angles (approximately a 90degrees apart from each other) when the device is in the initialdeflection stage just after the guard member 32 has been released fromengagement with the locking arm 40 b. As a more specific example, thelock ring 40 has rotated such that the ridge 40 c has just clearedlocking rib 32 k, thereby allowing the guard member 32 to more freelydeflect (in the proximal direction). At this point in the sequence, theinjection sequence likely has not been activated. For example, theplunger biasing member 50 likely has not yet been released, as thehousing 12 has not yet traveled distally enough for the delivery member16 to pierce the user's tissue.

In order for the components of the device to move from the stage shownin FIG. 14 to the stage shown in FIGS. 15A and 15B, two main events haveoccurred generally simultaneously with each other: initial rotation ofthe lock ring 40 and release from the locking arm 40 b. With respect tothe initial rotation, as shown in FIG. 15B, the lock ring cammingsurface 40 a is generally aligned with camming rib 32 j to converttranslational movement of the shield guard 32 into rotational movementof the lock ring 40. As a more specific example, as the shield guard isretracted the proximally facing top surface of the camming rib 32 japplies an axial upward force on the camming surface 40 a. As a morespecific example, the angle of the camming surface 40 a with respect tothe axis A causes the upward force from the camming rib 32 j to have anaxial component (along axis A) as well as a rotational component(transverse to axis A), thereby rotating the lock ring 40. In otherwords, in both the stage shown in FIG. 14 and the stage shown in FIG.15A and 15B, deflection (retraction) of the guard member 32 causesrotation of the lock ring 40. At the same time that camming rib 32 j isurging the lock ring 40 to rotate to the right (i.e. counter-clockwisewhen viewed from the top of FIG. 15B), the locking arm 40 b may begenerally resisting such movement. For example, when the guard member 32is depressed, it moves from the position shown in FIG. 14 to theposition shown in FIG. 15A and 15B. As a more specific example, when thedevice 10 is in position shown in FIG. 14, the ridge 40 c is disposed tothe left of the inertial rib 32 k such that the lock ring 40 is unableto rotate past a certain point until the ridge 40 c is able to clear theinertial rib 32 k. The ridge 40 c may be able to clear the inertial rib32 k via radially inward deflection of the locking arm 40 b, as is shownin FIG. 15A. In such a design, the flex of the locking arm 40 b at leastpartially determines the force required for the ridge 40 c to clear theinertial rib 32 k. In other words, the flex of the locking arm 40 b atleast partially determines the force required to deflect the guardmember 32 sufficiently to activate the injection process. The angle ofthe ridge 40 c with respect to the circumference of the lock ring 40 mayalso, in part, determine the force required to deflect the guard member32 sufficiently to activate the injection process. Additionally, thedegree of rotation that the lock ring 40 must undergo for the ridge 40 cto clear the inertial rib 32 k at least partially determines thedistance that the guard member 32 will translate (axially) before thelocking arm 40 b “releases” the guard member 32.

During operation, when the patient presses the distal end of the guardmember 32 against the patient's skin at the injection site, the deliverydevice 10 housing 12 may advance toward the injection site by arelatively small distance (e.g. 2-4 mm). The patient may then feelresistance between the inertial rib 32 k and the ridge 40 c. As thepatient presses down with more force, the ridge 40 c will clear theinertial rib 32 k and the delivery device 10 will achieve a quickrelease to harness the energy stored in the patient's muscles whilecompressing the needle cover and its spring to a defined release point.The release mechanism, such as the above-described flex of the lockingarm 40 b, the degree of rotation required to clear the inertial rib 32,and other parameters, may be designed such that when the ridge 40 cclears the inertial rib 32 k, the resulting needle insertion speedexceeds the patient's reaction speed, and the combination of this speedand the device's mass cause the needle to quickly and fully penetratethe skin to the subcutaneous depth. In other words, once the guardmember 32 reaches the position shown in FIGS. 15A and 15B, theresistance to depressing the guard member drops significantly so thatthe needle is inserted before the patient is able to halt the insertionprocess. As a more specific example, at this stage in the insertionprocess, the primary resistance to deflection of the guard member 32that is attributable to the components in the distal portion of thedevice is from the lock ring biasing member 51, but that resistance issignificantly lower than that provided by the locking arm 40 b. Also, ofnote, the user may still feel resistance against deflection of the guardmember 32 that is attributable to other subcomponents in the device,such as activation of the drive mechanism 30. Even though the insertionprocess occurs very quickly from this point forward, the subsequentstages will be examined in detail in the figures and the below text.

FIGS. 16A and 16B show views from different angles (approximately a 90degrees apart from each other) when the device is in the continueddownward travel stage (a later point in time than FIG. 15A and 15B,where the housing has moved further in the distal direction and theguard member 32 has been further retracted). At the point in thesequence shown in FIGS. 16A and 16B, the injection sequence may or maynot have begun, depending on the desired release parameters such asneedle length, desired insertion depth, distance between the guardmember 32 and the tip of the needle.

As shown in FIG. 16A, at this point in the sequence, the camming rib 32j of the guard member 32 clears or is about to clear the camming surface40 a so that the guard member 32 is able to deflect without rotating thelock ring 40. Additionally or alternatively, a ramped surface 40 e ofthe lock ring 40 may engage a ramped surface 12 g of the housing 12(that may be defined by the annular collar 12 d, similar or the same asthe ramped surface 412 g in FIG. 25); this interaction between therespective surfaces 40 e, 12 g may also promote rotation of the lockring 40 until it reaches the point shown in FIGS. 16A and 16B.Additionally or alternatively, at this stage of the insertion, a stopridge 40 f of the lock ring 40 engages a stop rib 32 n and limitsrotation of the lock ring 40. However, as discussed above, at this stagethe guard member 32 is able to deflect without requiring or causingfurther rotation of the lock ring 40. More specifically, as shown inFIGS. 16B and 17, the adjacent ribs (the stop rib 32 n and the cammingrib 32 j) extend between the adjacent components of the lock ring 40(the stop ridge 40 f and the camming surface 40 a) so that the guardmember 32 is able to deflect with respect to the housing 12.

FIG. 17 shows a view when the device is in the final insertion stage,when the guard member is fully or nearly fully retracted. At this pointin the sequence, the injection sequence likely has been activated. Forexample, the plunger biasing member 50 likely has been released and thedelivery member 16 has been inserted into the users tissue.Additionally, at this point in the sequence, the guard member 32 is ator near its fully retracted position with respect to the housing 12 andthe device 10 is still being held against the patient's skin. The userwill preferably hold the device 10 in this position until at least thetime when the drug delivery process is complete (i.e., when the fulldose of the drug 22 has been delivered to the patient) and theend-of-dose notification indicates that the dose is complete. Of note,for illustrative purposed, the guard member 32 shown in FIG. 17 hasportions cut-away and FIG. 17 does not show the housing 12 (includingthe annular collar) or the drug storage container 20.

FIGS. 18A and 18B shows the device 10 in a locked-out configuration,when the guard member 32 is in the fully extended position (FIG. 18A) ornear-fully extended position (FIG. 18B). As a more specific example, thestop rib 32 n and the camming rib 32 j of the guard member 32 arealigned with the stop ridge 40 f to limit and/or prevent deflection ofthe guard member 32 in the proximal direction. As another more specificexample, the guard member 32 is only able to travel in the proximaldirection by the distance shown by gap 91 in FIG. 18A so that the guardmember 32 is unable to be moved axially in the proximal direction by adistance sufficient to expose the delivery member 16. In other words,the guard member 32 is locked in a guarded position annularlysurrounding the needle and minimizing or preventing inadvertent needlesticks.

In some embodiments, prior to removal of the removable cap 19, thegripper 13 may be configured to prevent deflection of the locking arm 40b. As an example, an outer surface of the gripper 13 may be configuredto abut against an inner surface of the locking arm 40 b to preventradially inward deflection of the locking arm 40 b prior to removal ofthe removable cap 19. This configuration may reduce the possibility ofunintended lockout caused by vibrations or sudden movements duringtransport or storage of the drug delivery device 10 prior to use. Whenthe removable cap 19 with the gripper 13 is removed, the locking arm 40b may be allowed to deflect in the manner described above.

The lock ring 40 and the housing 12 have respective stop surfaces thatabut each other and prevent rotation therebetween. For example, the lockring 40 may have stop surfaces 40 g and 40 h (FIGS. 18A, 13) that abutstop surfaces 12 j, 12 k (FIG. 18A) of the annular collar 12 d. Therespective stop surfaces 40 g, 40 h of the lock ring 40 and therespective stop surfaces 12 j, 12 k of the annular collar 12 d may bestepped surfaces to prevent or resist rotation between the lock ring 40and the housing 12. The lock ring biasing member 51 may urge the lockring 40 in the proximal direction and/or the guard member 32 in thedistal direction to retain the lock ring 40 in place as shown in FIGS.18A and 18B, namely abutting the annular collar 12 d.

The circular cross-section of the housing 12 may make it prone torolling across a surface when placed on its side. To inhibit or preventsuch rolling, a portion or the entirety of the removable cap 19 may havea non-circular cross-section. In the embodiment illustrated in thefigures, the removable cap 19 has a distal end with a non-circularcross-section and a proximal end with a circular cross-section. As such,the cross-section of the removable cap 19 gradually transitions from acircular cross-section to a non-circular cross-section when moving fromthe proximal end of the removable cap 19 to the distal end of theremovable cap 19. In the illustrated embodiment, the non-circularcross-section of the distal end of the removable cap 19 generally takesthe form of a square. In other embodiments, the non-circularcross-section may be rectangular, triangular, or any other polygonal orpartially polygonal shape, so long one or more sides removable cap 19are flat or substantially flat to inhibit or prevent rolling.Furthermore, the non-circular cross-section of the distal end of theremovable cap 19 may gradually increase in size moving in the distaldirection, such that the distal-most portion of the distal end of theremovable cap 19 has a larger cross-sectional area than a proximal-mostportion of the distal end of the removable cap 19. This configurationgives the distal end of the removable cap 19 a flared shape, which, inturn, may help a user grip and pull the removable cap 19 off of thehousing 12.

In some embodiments, the housing 12 and the removable cap 19 may eachinclude a respective anti-rotation feature. These anti-rotation featuresmay engage each other to prevent or inhibit the removable cap 19 fromrotating relative to the housing 12 when the removable cap 19 is in astorage position. In some embodiments, the anti-rotation feature of thehousing 12 may be adjacent to and generally in-line with theanti-rotation feature of the removable cap 19 when the removable cap 19is in the storage position. For example, a radial protrusion 9 shown inFIG. 1A is positioned adjacent to the distal end of the housing 112. Asshown in FIG. 1B, the removable cap 19 includes an opening 8 may besized to matingly receive the radial protrusion 9 when the removable cap19 is in the storage position. As a consequence of this matingengagement, the removable cap 19 may be unable to rotate relative to thehousing 12. This may be beneficial if a user attempts to twist theremovable cap 19 when pulling the removable cap 19 off of the housing12. In certain cases, rotation of the removable cap 19 may cause asterile barrier such as an RNS or FNS to rotate, which, in turn, maycause a tip of a needle to core into a seal member within the RNS orFNS. Thus, having the radial protrusion 9 disposed within the opening 8at least during the initial moments of cap removal may prevent coring ofthe needle. In alternative embodiments, the opening 8 may be formed inthe wall of the housing 12 and the radial protrusion 9 may extend in theproximal direction from a proximal end of the removable cap 19.

In other embodiments, the removable cap may be permitted and/or intendedto rotate with respect to the housing. For example, the removable capmay include feature(s) that translate rotational movement of theremovable cap into an axial assist force that helps urge the cap awayfrom the housing. As a more specific example, the removable cap and/orthe housing may have a camming surface, such as a wave-shaped surface,that converts rotational movement of the removable cap with respect tothe housing into distal axial movement of the removable cap with respectto the housing. The axial assist force provided by such an arrangementmay benefit various users including those having limited dexterityand/or strength due to, for example, an illness.

FIGS. 19A-19B each show an exemplary force profile during the injectionprocess of an exemplary drug delivery device, where relativedisplacement between the device housing and the guard member is plottedalong the x-axis (in millimeters) and resistance is plotted along they-axis (Newtons). For example, the displacement (along the x-axis) showsthe relative axial displacement along axis A between the guard member 32and the housing 12. As discussed above, this relative axial displacementmay be understood to refer to translational movement of the housing 12with respect to the guard member 32 (such as in the case where a userurges the housing in the distal direction towards the users injectionsite while the user's tissue prevents the guard member 32 from moving inthe same direction) or it may be understood to refer to translationalmovement of the guard member 32 with respect to the housing (such as inthe case where the housing 12 is held in place and a user pushes on theguard member 32 in the proximal direction). In any event, the x-axis(horizontal) of the graph in FIG. 19 shows relative displacement betweenthe guard member 32 and the housing 12. The y-axis (vertical) of thegraph in FIG. 19 shows the resistance force during the various points ofrelative displacement between the guard member 32 and the housing 12.For example, at the point where the guard member 32 and housing 12 haveexperienced approximately 2 mm of relative displacement, the resistanceforce experienced by the user is approximately 7.75N for the forceprofile shown in FIG. 19A. As an even more specific example, theresistance force may refer to the force experienced by a user due tomechanical interactions between components of the device. For example,when first urging the housing 12 towards the injection site during thepre-injection state shown in FIG. 14, the resistance force is generallyequal to the force required to compress spring 51 as well as the forcerequired to urge the inertial rib 32 k past the ridge 40 c. The forceprofile in FIGS. 19A-19B show several exemplary, potential desired forceand displacement values, and thus it is understood that these values mayvary depending on the design of the previously-noted interactions.

Nonetheless, as shown in the exemplary force profile in FIG. 19A, theinitial resistance force is relatively low for the first approximately 1mm of travel between the guard member 32 and the housing, whereupon atpoint 202 the resistance force quickly increases (primarily due to theforce required to urge the inertial rib 32 k past the ridge 40 c) to apeak resistance force at point 204. Once the inertial rib 32 k hascleared the ridge 40 c (FIG. 15A), the resistance force quicklydecreases to point 206, where the resistance force is primarily due toforces required to compress spring 51 (FIG. 14), forces required tocompress spring 35 (FIG. 11B), and frictional forces between variousmoving components within the device. At point 208 the needle is insertedinto the users tissue and at point 210 the injection stage commences andthe drug 22 is injected into the user's tissue. Once the user overcomesthe peak resistance force at point 204, the user's inertia may drive thehousing and the drug storage container toward the injection site,prompting the needle insertion. This stage of the injection (betweenpoint 204 and 208) may occur over a relatively short period of time, dueto the user's inertia, to increase the likelihood that the needle isfully inserted rather than partially inserted and to decrease thelikelihood that the user stops movement of the device before or duringpartial needle insertion. In other words, once the user clears the peakresistance force at point 204, the user may have “committed” to theneedle insertion and/or the injection process.

FIG. 19B shows another exemplary force profile, where the peak force(point 304) is lower than the corresponding point (204) in FIG. 19A soas to require a lower initial force for the user to commit to theinsertion. This force profile may make the user less likely to stop theprocess during the initial depression (point 302), such as prematurelyremoving the device from the tissue. However, it may be desirable tohave the peak force 304 high enough to reduce the likelihood that theuser stops the injection between the peak force 304 and the needleinsertion 308. In other words, the vertical distance (along the y-axis)between points 304 and 308 should be large enough to cause this stage ofthe injection to occur over a relatively short period of time.

FIGS. 20A through 20G show a distal portion of an alternative design ofa device 400, primarily showing a housing 412, a guard member 432, alock ring 440, and a lock ring biasing member 451. As shown in FIGS. 20Aand FIG. 22, the guard member 432 includes an annular base portion 432a, a pair of longitudinally-extending arms 432 b, a ridge 432 h, aplurality of inner ribs (discussed in more detail below), and at leastone opening 432 x (also referred to as a hole in the annotations to someof the figures) formed through at least one of the ribs and a wall ofthe guard member. The opening 432 x need not be an opening formedthrough the entire wall of the guard member 432. For example, theopening may be merely a disconnection in the long rib or a protrusionsection with a shorter height rather than a cut-out of the wall of theguard member 432 and a portion of the rib. The inner ribs of the guardmember 432 include a first rib that is preferably longer than the otherribs (a.k.a. the long rib 432 r), and a pair of shorter ribs 432 s, 432t. The opening 432 x is formed through the long rib 432 r and is alignedwith and sized such as to selectively receive a component of the lockring 440, as will be discussed further below. As shown in FIGS. 20A andFIG. 23, the lock ring 440 includes a plurality of stop surfaces 440 g,440 h, a U-shaped projection 440 w (configured to be received within theopening 432 x), and plurality of proximally-facing cam surfaces 440 x,440 y. However, the lock ring 440 shown in FIGS. 20A and 23 does nothave distally-facing cam surfaces corresponding to surface 40 a in thedesign shown in FIG. 13. As shown in FIG. 20A, during a pre-injection,non-deflection state of the device 400, each of the two U-shapedprojections 440 w are not initially received within the openings 432 x.Rather, at this point, the proximal portion of the long rib 432 r (i.e.the portion of the long rib that is proximal of the opening 432 x) isreceived within the U-shaped projection 440 w such as to prevent thelock ring from moving upwards (proximal direction) with respect to theguard member. As the housing 412 moves downward (distally) and/or theguard member 432 moves upward (proximally), as shown in FIG. 20B, thelock ring 440 is able to move upward (proximally) from the spring 451,thereby causing cam surfaces on the housing 412 to contact the lock ringcamming surfaces 440 x, 440 y and rotationally urge the lock ring. Atthe stage shown in FIG. 20B, the lock ring 440 is unable to rotate dueto the proximal portion of the long rib 432 r being alignedwith/received within the U-shaped projection 440 w. Also as shown inFIG. 20B, the housing cam surface 412 x engages the lock ring camsurface 440 y. However, as the relative movement between the guardmember and the housing progresses to the state shown in FIG. 20C, theengagement between the housing cam surface 412 x and the lock ring camsurface 440 y, combined with further relative movement between the guardmember and the housing cause the following: (1) the engagement betweenthe housing cam surface 412 x and the lock ring cam surface 440 y haltsupward movement of the lock ring so that the proximal portion of thelong rib 432 r is able to move out of alignment with/engagement with theU-shaped projection 440 such that the U-shaped projection 440 w is nowaligned with the opening 432 x and (2) the respective cam surfaceengagement 412 x, 440 y causes the lock ring 440 to rotate. As shown inFIG. 20D, the lock ring rotates to a point (roughly two-thirds of itstotal rotation) where it is now rotationally constrained by the shortribs 432 s, 432 t in the guard member (more specifically, a stop surface440 v shown in FIG. 23 engages the short ribs 432 s, 432 t). In thestate shown in FIG. 20E, the guard member arms 432 b sufficiently moverelative to the housing 412 such that the injection sequence initiates.As shown in FIG. 20F, once the user releases pressure on the housing andpermits relative proximal movement of the housing and/or distal movementof the guard member, the lock ring is rotationally constrained untilstop surface 440 v clears the short ribs 432 s, 432 t and the lock ringrotates into a lock out configuration shown in FIG. 20G.

FIGS. 26A through 26D show another alternative design of a device 600,primarily showing a housing 612, a guard member 632, a lock ring 640,and a lock ring biasing member 651. As shown in 26C, the guard member632 includes an annular base portion 632 a, a pair oflongitudinally-extending arms 632 b, a ridge 632 h, a plurality of innerribs (discussed in more detail below), and at least one opening 632 x(also referred to as a hole herein) formed through at least one of theribs and a wall of the guard member. Each of the ribs of the guardmember 632 may be configured as a radially inwardly extendingprotrusion. The opening 632 x need not be an opening formed through theentire wall of the guard member 632. For example, the opening 632 x maybe merely a disconnection in the long rib or a protrusion section with ashorter height rather than a cut-out of the wall of the guard member 632and a portion of the rib. The opening 632 x is formed through rib 632 rand is aligned with and sized such as to selectively receive a componentof the lock ring 640, as will be discussed further below. As shown inFIGS. 26A, 26B, and 26D, the lock ring 640 includes a plurality of stopsurfaces 640 g, 640 h, at least one tab-shaped projection 640 w(configured to be received within the opening 632 x), and plurality ofproximally-facing camming surfaces 640 y. As illustrated in FIG. 26A,each tab-shaped projection 640 w may be configured as a radiallyoutwardly extending protrusion and may include proximally-facing cammingsurface 640 z. As shown in FIG. 26D, during a pre-injection,partial-deflection state of the device 600, each of the two tab-shapedprojections 640 w are not initially received within the openings 632 x.Rather, at this point, a proximally-facing camming surface 612 x ofhousing 612 engages the distally-facing camming surface 640 y of thelock ring 640 to prevent or resist the lock ring 640 from moving upwards(proximal direction) with respect to the guard member 632. At the sametime, the tab-shaped projections 640 w are each respectively engagedwith a pair of ramp surfaces 632 y (also referred to herein asproximally-facing camming surfaces 632 y). At this stage of theinjection, the guard member 632 has been partially deflected (such as inFIG. 20B) but the lock ring 640 has not yet rotated and the guard member632 has not yet moved upwards a distance sufficient to initiate theinjection sequence. At this point, the user will feel a resistance tofurther movement of the injector housing 612, due to the respectiveengagements described above, namely the proximally-facing cammingsurface 612 x of the housing 612 with the distally-facing cammingsurface 640 y of the lock ring 640 and the proximally-facing cammingsurface 640 z of the tab-shaped projection 640 w of the lock ring 640with the guard member ramp surface 632 y. This resistance may or likelywill prompt the user to press down on the injector with a forcesufficient to overcome the resistance (i.e. the peak resistance of theinjector). The peak resistance is caused by the aforementionedinteractions (the distally-facing camming surface 612 x of the housing612 with the proximally-facing camming surface 640 y of the lock ring640 and the distally-facing camming surface 640 z of the tab-shapedprojection 640 w of the lock ring 640 with the guard member ramp surface632 y) and it is overcome (i.e. released) when the users force issufficient such that the tab-shaped projection 640 w of the lock ring640 slides along the guard member ramped surface 632 y and theproximally-facing camming surface 640 y of the lock ring 640 will slidealong the distally-facing camming surface 612 x of the housing 612 (tothe left in FIG. 26D). In other words, the lock ring 640 will rotate inthe direction of arrow 601 and will travel slightly downward (distally)shown in FIG. 26D. Once the lock ring 640 rotates enough so that thelock ring tab-shaped projection 640 w has cleared the guard memberramped surface 632 y, the guard member 632 will be able to move axiallyupward (proximally). At this point, two things will happen: (1) theguard member 632 will translate in the proximal direction a sufficientdistance such as to initiate the injection sequence and (2) the lockring tab-shaped projection 640 w will become axially aligned with guardmember opening 632 x (FIG. 26C) and thereby allow the lock ring 640 torotate in the direction of arrow 602 (FIG. 26D) and slightly upwards(proximal direction) due to the interaction between theproximally-facing camming surface 640 y of the lock ring 640 and thedistally-facing camming surface 612 x of the housing 612. After theinjection is initiated, the lock ring 640 will be in a position where itcan lock-out the shield, similar to the other embodiments describedabove. The injector 600 may be designed such that events (1) and (2)occur simultaneously, so that once the guard member translates adistance sufficient to initiate the injection, the lock ring will rotatean angle sufficient to initiate the lock-out sequence. This may bedesirable to substantially or completely prevent a user from attemptingto perform multiple injections. This may also be desirable tosubstantially or completely prevent the lock-out sequence frominitiating without the injection sequence also initiating. In otherwords, the above configuration may reduce the likelihood that a user hasa locked-out injector with an undelivered dose.

To facilitate rotation of the lock ring 640 relative to the housing 612and/or the guard member 632, any two or combination of the following maybe parallel to each other: the distally-facing camming surface(s) 612 xof the housing 612, the proximally-facing camming surface(s) 632 y ofthe guard member 632, the distally-facing camming surface(s) 640 z ofthe lock ring 640, and the proximally-facing camming surface(s) 640 y ofthe lock ring 640.

FIGS. 21A through 21F show a distal portion of another alternativedesign of a device 500, primarily showing a housing 512, a guard member532, a lock ring 540, and a lock ring biasing member 551. The componentsof the device 500 are similar to those on the device 400, except thatinstead of the U-shaped projection 440 w, the lock ring 540 has only apair of parallel projections 540 w that do not have a horizontalprojection connecting them. In other words, the projections 540 w havethe “side portions” of a U-shape but do not have the “bottom portion” ofa U-shape. In the state shown in FIG. 21A, the projections 540 w arereceived within a long rib of the guard member 532 to prevent rotationalmovement of the lock ring. As relative movement occurs between the guardmember and the housing, as shown in FIG. 21B, the projections 540 wbecome aligned with an opening in the guard member, thereby allowingrotational movement of the lock ring with respect to the guard member(and urged by a camming surface on the housing). As shown in the statein FIG. 21C, the lock ring then rotates until stop surface 440 v engagesthe short ribs in the guard member. FIG. 21D shows the distal componentsof the device during the injection activation. FIG. 21E shows the stateof the distal components once the user has released pressure and theguard member is able to move (extend distally) relative to the housing.FIG. 21F shows the lock-out configuration.

FIG. 24 provides a graph for comparing the force profiles illustrated inFIGS. 19A and 19B with force profiles attributable to the drug deliverydevice 400 shown in FIGS. 20A-20G and the drug delivery device 500 shownin FIGS. 21A-21F. Similar to FIGS. 19A and 19B, FIG. 24 plots theresistance force experienced by a user versus displacement of a shield(e.g., the shield guard 32). Additionally, FIG. 24 identifies where ineach force profile a lock point associated with a lock ring is designedto occur. FIG. 24 shows that the lock point for the force profiles inFIGS. 19A and 19B occurs at the same shield displacement as when theuser experiences a peak resistance. By contrast, the lock point for theforce profiles associated with drug delivery devices 400 and 500 doesnot coincide with a shield displacement corresponding to a peakresistance experienced by the user.

Continuing with FIG. 24, the force profile associated with the drugdelivery device 400 is similar to the force profiles in FIGS. 19A and19B in that prior to needle insertion the user experiences a sudden jumpin resistance caused by displacing the shield. Unlike the force profilesin FIGS. 19A and 19B, the resistance experienced by the user of the drugdelivery device 400 may continue to increase after this jump (until theactivation point). FIG. 24 shows that the user of the drug deliverydevice 500 may not experience a sudden jump in resistance during shielddisplacement but rather may experience a gradual increase in resistanceuntil the activation point. A manufacturer may choose one of the forceprofiles illustrated in FIG. 24 or a different force profiles dependingon, for example, a desired user experience, physical and/or mentalabilities of a target user or patient population, mechanical safetyconsiderations, and/or additional considerations.

From the foregoing, it can be seen that the present disclosureadvantageously provides a streamlined design for a drug delivery devicehaving automated features. Various mechanisms and components of the drugdelivery device may interact with each other in synergistic ways so asto limit the number of moving parts required by the drug deliverydevice, thereby improving the reliability of the drug delivery deviceand saving costs, as well as providing other benefits and advantages.

As will be recognized, the devices and methods according to the presentdisclosure may have one or more advantages relative to conventionaltechnology, any one or more of which may be present in a particularembodiment in accordance with the features of the present disclosureincluded in that embodiment. Other advantages not specifically listedherein may also be recognized as well.

The above description describes various devices, assemblies, components,subsystems and methods for use related to a drug delivery device. Thedevices, assemblies, components, subsystems, methods or drug deliverydevices can further comprise or be used with a drug including but notlimited to those drugs identified below as well as their generic andbiosimilar counterparts. The term drug, as used herein, can be usedinterchangeably with other similar terms and can be used to refer to anytype of medicament or therapeutic material including traditional andnon-traditional pharmaceuticals, nutraceuticals, supplements, biologics,biologically active agents and compositions, large molecules,biosimilars, bioequivalents, therapeutic antibodies, polypeptides,proteins, small molecules and generics. Non-therapeutic injectablematerials are also encompassed. The drug may be in liquid form, alyophilized form, or in a reconstituted from lyophilized form. Thefollowing example list of drugs should not be considered asall-inclusive or limiting.

The drug will be contained in a reservoir. In some instances, thereservoir is a primary container that is either filled or pre-filled fortreatment with the drug. The primary container can be a vial, acartridge or a pre-filled syringe.

In some embodiments, the reservoir of the drug delivery device may befilled with or the device can be used with colony stimulating factors,such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF agentsinclude but are not limited to Neulasta® (pegfilgrastim, pegylatedfilgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF) and Neupogen®(filgrastim, G-CSF, hu-MetG-CSF), UDENYCA® (pegfilgrastim-cbqv),Ziextenzo® (LA-EP2006; pegfilgrastim-bmez), or FULPHILA(pegfilgrastim-bmez).

In other embodiments, the drug delivery device may contain or be usedwith an erythropoiesis stimulating agent (ESA), which may be in liquidor lyophilized form. An ESA is any molecule that stimulateserythropoiesis. In some embodiments, an ESA is an erythropoiesisstimulating protein. As used herein, “erythropoiesis stimulatingprotein” means any protein that directly or indirectly causes activationof the erythropoietin receptor, for example, by binding to and causingdimerization of the receptor. Erythropoiesis stimulating proteinsinclude erythropoietin and variants, analogs, or derivatives thereofthat bind to and activate erythropoietin receptor; antibodies that bindto erythropoietin receptor and activate the receptor; or peptides thatbind to and activate erythropoietin receptor. Erythropoiesis stimulatingproteins include, but are not limited to, Epogen® (epoetin alfa),Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxypolyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22,Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetinzeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetinalfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin®(epoetin theta), epoetin alfa, epoetin beta, epoetin iota, epoetinomega, epoetin delta, epoetin zeta, epoetin theta, and epoetin delta,pegylated erythropoietin, carbamylated erythropoietin, as well as themolecules or variants or analogs thereof.

Among particular illustrative proteins are the specific proteins setforth below, including fusions, fragments, analogs, variants orderivatives thereof: OPGL specific antibodies, peptibodies, relatedproteins, and the like (also referred to as RANKL specific antibodies,peptibodies and the like), including fully humanized and human OPGLspecific antibodies, particularly fully humanized monoclonal antibodies;Myostatin binding proteins, peptibodies, related proteins, and the like,including myostatin specific peptibodies; IL-4 receptor specificantibodies, peptibodies, related proteins, and the like, particularlythose that inhibit activities mediated by binding of IL-4 and/or IL-13to the receptor; Interleukin 1-receptor 1 (“IL1-R1”) specificantibodies, peptibodies, related proteins, and the like; Ang2 specificantibodies, peptibodies, related proteins, and the like; NGF specificantibodies, peptibodies, related proteins, and the like; CD22 specificantibodies, peptibodies, related proteins, and the like, particularlyhuman CD22 specific antibodies, such as but not limited to humanized andfully human antibodies, including but not limited to humanized and fullyhuman monoclonal antibodies, particularly including but not limited tohuman CD22 specific IgG antibodies, such as, a dimer of a human-mousemonoclonal hLL2 gamma-chain disulfide linked to a human-mouse monoclonalhLL2 kappa-chain, for example, the human CD22 specific fully humanizedantibody in Epratuzumab, CAS registry number 501423-23-0; IGF-1 receptorspecific antibodies, peptibodies, and related proteins, and the likeincluding but not limited to anti-IGF-1R antibodies; B-7 related protein1 specific antibodies, peptibodies, related proteins and the like(“B7RP-1” and also referring to B7H2, ICOSL, B7h, and CD275), includingbut not limited to B7RP-specific fully human monoclonal IgG2 antibodies,including but not limited to fully human IgG2 monoclonal antibody thatbinds an epitope in the first immunoglobulin-like domain of B7RP-1,including but not limited to those that inhibit the interaction ofB7RP-1 with its natural receptor, ICOS, on activated T cells; IL-15specific antibodies, peptibodies, related proteins, and the like, suchas, in particular, humanized monoclonal antibodies, including but notlimited to HuMax IL-15 antibodies and related proteins, such as, forinstance, 145c7; IFN gamma specific antibodies, peptibodies, relatedproteins and the like, including but not limited to human IFN gammaspecific antibodies, and including but not limited to fully humananti-IFN gamma antibodies; TALL-1 specific antibodies, peptibodies,related proteins, and the like, and other TALL specific bindingproteins; Parathyroid hormone (“PTH”) specific antibodies, peptibodies,related proteins, and the like; Thrombopoietin receptor (“TPO-R”)specific antibodies, peptibodies, related proteins, and the like;Hepatocyte growth factor (“HGF”) specific antibodies, peptibodies,related proteins, and the like, including those that target theHGF/SF:cMet axis (HGF/SF:c-Met), such as fully human monoclonalantibodies that neutralize hepatocyte growth factor/scatter (HGF/SF);TRAIL-R2 specific antibodies, peptibodies, related proteins and thelike; Activin A specific antibodies, peptibodies, proteins, and thelike; TGF-beta specific antibodies, peptibodies, related proteins, andthe like; Amyloid-beta protein specific antibodies, peptibodies, relatedproteins, and the like; c-Kit specific antibodies, peptibodies, relatedproteins, and the like, including but not limited to proteins that bindc-Kit and/or other stem cell factor receptors; OX40L specificantibodies, peptibodies, related proteins, and the like, including butnot limited to proteins that bind OX40L and/or other ligands of the OX40receptor; Activase® (alteplase, tPA); Aranesp® (darbepoetin alfa)Erythropoietin [30-asparagine, 32-threonine, 87-valine, 88-asparagine,90-threonine], Darbepoetin alfa, novel erythropoiesis stimulatingprotein (NESP); Epogen® (epoetin alfa, or erythropoietin); GLP-1,Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonalantibody); Betaseron® (interferon-beta); Campath® (alemtuzumab,anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade®(bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokinereceptor mAb); Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNFblocker); Eprex® (epoetin alfa); Erbitux® (cetuximab,anti-EGFR/HER1/c-ErbB-1); Genotropin® (somatropin, Human GrowthHormone); Herceptin® (trastuzumab, anti-HER2/neu (erbB2) receptor mAb);Kanjinti™ (trastuzumab-anns) anti-HER2 monoclonal antibody, biosimilarto Herceptin®, or another product containing trastuzumab for thetreatment of breast or gastric cancers; Humatrope® (somatropin, HumanGrowth Hormone); Humira® (adalimumab); Vectibix® (panitumumab), Xgeva®(denosumab), Prolia® (denosumab), Immunoglobulin G2 Human MonoclonalAntibody to RANK Ligand, Enbrel® (etanercept, TNF-receptor/Fc fusionprotein, TNF blocker), Nplate® (romiplostim), rilotumumab, ganitumab,conatumumab, brodalumab, insulin in solution; Infergen® (interferonalfacon-1); Natrecor® (nesiritide; recombinant human B-type natriureticpeptide (hBNP); Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF);LymphoCide® (epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B,belimumab, anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog);Mircera® (methoxy polyethylene glycol-epoetin beta); Mylotarg®(gemtuzumab ozogamicin); Raptiva® (efalizumab); Cimzia® (certolizumabpegol, CDP 870); Solids™ (eculizumab); pexelizumab (anti-C5 complement);Numax® (MEDI-524); Lucentis® (ranibizumab); Panorex® (17-1A,edrecolomab); Trabio® (lerdelimumab); TheraCim hR3 (nimotuzumab);Omnitarg (pertuzumab, 2C4); Osidem® (IDM-1); OvaRex® (B43.13); Nuvion®(visilizumab); cantuzumab mertansine (huC242-DM1); NeoRecormon® (epoetinbeta); Neumega® (oprelvekin, human interleukin-11); Orthoclone OKT3®(muromonab-CD3, anti-CD3 monoclonal antibody); Procrit® (epoetin alfa);Remicade® (infliximab, anti-TNFα monoclonal antibody); Reopro®(abciximab, anti-GP IIb/IIia receptor monoclonal antibody); Actemra®(anti-IL6 Receptor mAb); Avastin® (bevacizumab), HuMax-CD4(zanolimumab); Mvasi™ (bevacizumab-awwb); Rituxan® (rituximab, anti-CD20mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2a); Simulect®(basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 145c7-CHO(anti-IL15 antibody, see U.S. Pat. No. 7,153,507); Tysabri®(natalizumab, anti-α4integrin mAb); Valortim® (MDX-1303, anti-B.anthracis protective antigen mAb); ABthrax™; Xolair® (omalizumab);ETI211 (anti-MRSA mAb); IL-1 trap (the Fc portion of human IgG1 and theextracellular domains of both IL-1 receptor components (the Type Ireceptor and receptor accessory protein)); VEGF trap (Ig domains ofVEGFR1 fused to IgG1 Fc); Zenapax® (daclizumab); Zenapax® (daclizumab,anti-IL-2Rα mAb); Zevalin® (ibritumomab tiuxetan); Zetia® (ezetimibe);Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonal antibody(galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3/huFc fusionprotein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFα mAb);HGS-ETR1 (mapatumumab; human anti-TRAIL Receptor-1 mAb); HuMax-CD20(ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab); M200(volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab, anti-CTLA-4mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C. difficile Toxin A andToxin B C mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22 dsFv-PE38conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333(anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-CriptomAb; anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-3019);anti-CTLA4 mAb; anti-eotaxin1 mAb (CAT-213); anti-FGF8 mAb;anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; anti-GDF-8 human mAb(MYO-029); anti-GM-CSF Receptor mAb (CAM-3001); anti-HepC mAb (HuMaxHepC); anti-IFNα mAb (MEDI-545, MDX-198); anti-IGF1R mAb; anti-IGF-1RmAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12/IL23 mAb (CNTO1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5Receptor mAb; anti-integrin receptors mAb (MDX-018, CNTO 95); anti-IP10Ulcerative Colitis mAb (MDX-1100); BMS-66513; anti-Mannose Receptor/hCGβmAb (MDX-1307); anti-mesothelin dsFv-PE38 conjugate (CAT-5001);anti-PD1mAb (MDX-1106 (ONO-4538)); anti-PDGFRα antibody (IMC-3G3);anti-TGFβ mAb (GC-1008); anti-TRAIL Receptor-2 human mAb (HGS-ETR2);anti-TWEAK mAb; anti-VEGFR/Flt-1 mAb; and anti-ZP3 mAb (HuMax-ZP3).

In some embodiments, the drug delivery device may contain or be usedwith a sclerostin antibody, such as but not limited to romosozumab,blosozumab, BPS 804 (Novartis), Evenity™ (romosozumab-aqqg), anotherproduct containing romosozumab for treatment of postmenopausalosteoporosis and/or fracture healing and in other embodiments, amonoclonal antibody (IgG) that binds human Proprotein ConvertaseSubtilisin/Kexin Type 9 (PCSK9). Such PCSK9 specific antibodies include,but are not limited to, Repatha® (evolocumab) and Praluent®(alirocumab). In other embodiments, the drug delivery device may containor be used with rilotumumab, bixalomer, trebananib, ganitumab,conatumumab, motesanib diphosphate, brodalumab, vidupiprant orpanitumumab. In some embodiments, the reservoir of the drug deliverydevice may be filled with or the device can be used with IMLYGIC®(talimogene laherparepvec) or another oncolytic HSV for the treatment ofmelanoma or other cancers including but are not limited toOncoVEXGALV/CD; OrienX010; G207, 1716; NV1020; NV12023; NV1034; andNV1042. In some embodiments, the drug delivery device may contain or beused with endogenous tissue inhibitors of metalloproteinases (TIMPs)such as but not limited to TIMP-3. In some embodiments, the drugdelivery device may contain or be used with Aimovig® (erenumab-aooe),anti-human CGRP-R (calcitonin gene-related peptide type 1 receptor) oranother product containing erenumab for the treatment of migraineheadaches. Antagonistic antibodies for human calcitonin gene-relatedpeptide (CGRP) receptor such as but not limited to erenumab andbispecific antibody molecules that target the CGRP receptor and otherheadache targets may also be delivered with a drug delivery device ofthe present disclosure. Additionally, bispecific T cell engager (BITE®)antibodies such as but not limited to BLINCYTO® (blinatumomab) can beused in or with the drug delivery device of the present disclosure. Insome embodiments, the drug delivery device may contain or be used withan APJ large molecule agonist such as but not limited to apelin oranalogues thereof. In some embodiments, a therapeutically effectiveamount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptorantibody is used in or with the drug delivery device of the presentdisclosure. In some embodiments, the drug delivery device may contain orbe used with Avsola™ (infliximab-axxq), anti-TNF α monoclonal antibody,biosimilar to Remicade® (infliximab) (Janssen Biotech, Inc.) or anotherproduct containing infliximab for the treatment of autoimmune diseases.In some embodiments, the drug delivery device may contain or be usedwith Kyprolis® (carfilzomib),(2S)-N-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylcarbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4-methylpentanamide, or anotherproduct containing carfilzomib for the treatment of multiple myeloma. Insome embodiments, the drug delivery device may contain or be used withOtezla® (apremilast),N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide,or another product containing apremilast for the treatment of variousinflammatory diseases. In some embodiments, the drug delivery device maycontain or be used with Parsabiv™ (etelcalcetide HCl, KAI-4169) oranother product containing etelcalcetide HCl for the treatment ofsecondary hyperparathyroidism (sHPT) such as in patients with chronickidney disease (KD) on hemodialysis. In some embodiments, the drugdelivery device may contain or be used with ABP 798 (rituximab), abiosimilar candidate to Rituxan®/MabThera™, or another productcontaining an anti-CD20 monoclonal antibody. In some embodiments, thedrug delivery device may contain or be used with a VEGF antagonist suchas a non-antibody VEGF antagonist and/or a VEGF-Trap such as aflibercept(Ig domain 2 from VEGFR1 and Ig domain 3 from VEGFR2, fused to Fc domainof IgG1). In some embodiments, the drug delivery device may contain orbe used with ABP 959 (eculizumab), a biosimilar candidate to Soliris®,or another product containing a monoclonal antibody that specificallybinds to the complement protein C5. In some embodiments, the drugdelivery device may contain or be used with Rozibafusp alfa (formerlyAMG 570) is a novel bispecific antibody-peptide conjugate thatsimultaneously blocks ICOSL and BAFF activity. In some embodiments, thedrug delivery device may contain or be used with Omecamtiv mecarbil, asmall molecule selective cardiac myosin activator, or myotrope, whichdirectly targets the contractile mechanisms of the heart, or anotherproduct containing a small molecule selective cardiac myosin activator.In some embodiments, the drug delivery device may contain or be usedwith Sotorasib (formerly known as AMG 510), a KRAS^(G12C) small moleculeinhibitor, or another product containing a KRAS^(G12C) small moleculeinhibitor. In some embodiments, the drug delivery device may contain orbe used with Tezepelumab, a human monoclonal antibody that inhibits theaction of thymic stromal lymphopoietin (TSLP), or another productcontaining a human monoclonal antibody that inhibits the action of TSLP.In some embodiments, the drug delivery device may contain or be usedwith AMG 714, a human monoclonal antibody that binds to Interleukin-15(IL-15) or another product containing a human monoclonal antibody thatbinds to Interleukin-15 (IL-15). In some embodiments, the drug deliverydevice may contain or be used with AMG 890, a small interfering RNA(siRNA) that lowers lipoprotein(a), also known as Lp(a), or anotherproduct containing a small interfering RNA (siRNA) that lowerslipoprotein(a). In some embodiments, the drug delivery device maycontain or be used with ABP 654 (human IgG1 kappa antibody), abiosimilar candidate to Stelara®, or another product that contains humanIgG1 kappa antibody and/or binds to the p40 subunit of human cytokinesinterleukin (IL)-12 and IL-23. In some embodiments, the drug deliverydevice may contain or be used with Amjevita™ or Amgevita™ (formerly ABP501) (mab anti-TNF human IgG1), a biosimilar candidate to Humira®, oranother product that contains human mab anti-TNF human IgG1. In someembodiments, the drug delivery device may contain or be used with AMG160, or another product that contains a half-life extended (HLE)anti-prostate-specific membrane antigen (PSMA)×anti-CD3 BiTE®(bispecific T cell engager) construct. In some embodiments, the drugdelivery device may contain or be used with AMG 119, or another productcontaining a delta-like ligand 3 (DLL3) CART (chimeric antigen receptorT cell) cellular therapy. In some embodiments, the drug delivery devicemay contain or be used with AMG 119, or another product containing adelta-like ligand 3 (DLL3) CART (chimeric antigen receptor T cell)cellular therapy. In some embodiments, the drug delivery device maycontain or be used with AMG 133, or another product containing a gastricinhibitory polypeptide receptor (GIPR) antagonist and GLP-1R agonist. Insome embodiments, the drug delivery device may contain or be used withAMG 171 or another product containing a Growth Differential Factor 15(GDF15) analog. In some embodiments, the drug delivery device maycontain or be used with AMG 176 or another product containing a smallmolecule inhibitor of myeloid cell leukemia 1 (MCL-1). In someembodiments, the drug delivery device may contain or be used with AMG199 or another product containing a half-life. extended (HLE) bispecificT cell engager construct (BITE®). In some embodiments, the drug deliverydevice may contain or be used with AMG 256 or another product containingan anti-PD-1×IL21 mutein and/or an IL-21 receptor agonist designed toselectively turn on the Interleukin 21 (IL-21) pathway in programmedcell death-1 (PD-1) positive cells. In some embodiments, the drugdelivery device may contain or be used with AMG 330 or another productcontaining an anti-CD33×anti-CD3 BiTE® (bispecific T cell engager)construct. In some embodiments, the drug delivery device may contain orbe used with AMG 404 or another product containing a humananti-programmed cell death-1(PD-1) monoclonal antibody beinginvestigated as a treatment for patients with solid tumors. In someembodiments, the drug delivery device may contain or be used with AMG427 or another product containing a half-life extended (HLE)anti-fms-like tyrosine kinase 3 (FLT3)×anti-CD3 BiTE® (bispecific T cellengager) construct. In some embodiments, the drug delivery device maycontain or be used with AMG 430 or another product containing ananti-Jagged-1 monoclonal antibody. In some embodiments, the drugdelivery device may contain or be used with AMG 506 or another productcontaining a multi-specific FAP×4-1BB-targeting DARPin® biologic underinvestigation as a treatment for solid tumors. In some embodiments, thedrug delivery device may contain or be used with AMG 509 or anotherproduct containing a bivalent T-cell engager and is designed using XmAb®2+1 technology. In some embodiments, the drug delivery device maycontain or be used with AMG 562 or another product containing ahalf-life extended (HLE) CD19×CD3 BiTE® (bispecific T cell engager)construct. In some embodiments, the drug delivery device may contain orbe used with Efavaleukin alfa (formerly AMG 592) or another productcontaining an IL-2 mutein Fc fusion protein. In some embodiments, thedrug delivery device may contain or be used with AMG 596 or anotherproduct containing a CD3×epidermal growth factor receptor vIII(EGFRvIII) BiTE® (bispecific T cell engager) molecule. In someembodiments, the drug delivery device may contain or be used with AMG673 or another product containing a half-life extended (HLE)anti-CD33×anti-CD3 BiTE® (bispecific T cell engager) construct. In someembodiments, the drug delivery device may contain or be used with AMG701 or another product containing a half-life extended (HLE) anti-B-cellmaturation antigen (BCMA)×anti-CD3 BiTE® (bispecific T cell engager)construct. In some embodiments, the drug delivery device may contain orbe used with AMG 757 or another product containing a half-life extended(HLE) anti-delta-like ligand 3 (DLL3)×anti-CD3 BiTE® (bispecific T cellengager) construct. In some embodiments, the drug delivery device maycontain or be used with AMG 910 or another product containing ahalf-life extended (HLE) epithelial cell tight junction protein claudin18.2×CD3 BiTE® (bispecific T cell engager) construct.

Although the drug delivery devices, assemblies, components, subsystemsand methods have been described in terms of exemplary embodiments, theyare not limited thereto. The detailed description is to be construed asexemplary only and does not describe every possible embodiment of thepresent disclosure. Numerous alternative embodiments could beimplemented, using either current technology or technology developedafter the filing date of this patent that would still fall within thescope of the claims defining the invention(s) disclosed herein.

Those skilled in the art will recognize that a wide variety ofmodifications, alterations, and combinations can be made with respect tothe above described embodiments without departing from the spirit andscope of the invention(s) disclosed herein, and that such modifications,alterations, and combinations are to be viewed as being within the ambitof the inventive concept(s).

1. A drug delivery device comprising: a housing defining a longitudinalaxis and having an opening; a drug storage container including adelivery member having an insertion end configured to extend at leastpartially through the opening during a delivery state; a plungermoveable toward the distal end of the drug storage container to expel adrug from the drug storage container through the delivery member, theplunger including a body portion having an inner wall defining an axialchamber and an outer wall cooperating with the inner wall to define abody thickness less than 0.6 millimeters; and a plunger biasing membercoupled with the plunger and configured to urge the plunger toward thedistal end of the drug storage container.
 2. The drug delivery device ofclaim 1, wherein the body thickness is less than 0.4 millimeters.
 3. Thedrug delivery device of claim 1, wherein the body thickness is less than0.3 millimeters.
 4. The drug delivery device of claim 1, wherein thebody thickness is less than 0.2 millimeters.
 5. The drug delivery deviceof claim 1, wherein the body thickness is less than 0.1 millimeters. 6.The drug delivery device of claim 1, wherein the body thickness is lessthan 0.05 millimeters.
 7. A drug delivery device comprising: a housingdefining a longitudinal axis and having an opening; a drug storagecontainer including a delivery member having an insertion end configuredto extend at least partially through the opening during a deliverystate; a plunger moveable toward the distal end of the drug storagecontainer to expel a drug from the drug storage container through thedelivery member, the plunger including a body portion having an innerwall defining an axial chamber and an outer wall cooperating with theinner wall to define a body thickness; and a plunger biasing memberdisposed at least partially within the axial chamber, the plungerbiasing member configured to urge the plunger toward the distal end ofthe drug storage container.
 8. The drug delivery device of claim 7,wherein the body portion has a hollow tubular shape.
 9. The drugdelivery device of claim 7, wherein the body portion is made of metal.10. The drug delivery device of claim 7, wherein the body portion ismade of a non-metal.
 11. The drug delivery device of claim 7, whereinthe plunger is configured to: selectively rotate from an initialrotational position to a second rotational position under a biasingforce exerted by the plunger biasing member, and translate linearlytoward the distal end of the drug storage container under the biasingforce exerted by the plunger biasing member after rotating from theinitial rotational position to the second rotational position.
 12. Thedrug delivery device of claim 7, further comprising a plunger guidefixed relative to the housing, the plunger being disposed at leastpartially within the plunger guide.
 13. The drug delivery device ofclaim 12, wherein one of the plunger and the plunger guide comprises acam and the other one of the plunger and the plunger guide comprises acam follower.
 14. The drug delivery device of claim 13, wherein theplunger includes the cam follower and the plunger guide includes thecam, and wherein the cam follower is formed by at least one flangeextending radially outwardly from the plunger.
 15. The drug deliverydevice of claim 7, wherein the body thickness is less than 0.6millimeters.
 16. The drug delivery device of claim 7, wherein the bodythickness is less than 0.4 millimeters.
 17. The drug delivery device ofclaim 7, wherein the body thickness is less than 0.3 millimeters. 18.The drug delivery device of claim 7, wherein the body thickness is lessthan 0.2 millimeters.
 19. The drug delivery device of claim 7, whereinthe body thickness is less than 0.1 millimeters.
 20. The drug deliverydevice of claim 7, wherein the body thickness is less than 0.05millimeters.